journal of science and research - Facultad de Medicina de la UANL

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Vol. 16 • Num. 64 • July-September 2014
Vol. 16 • Num. 64 • July-September 2014 • ISSN 1665-5796
JOURNAL OF SCIENCE AND RESEARCH
SCHOOL OF MEDICINE AND “DR. JOSÉ ELEUTERIO GONZÁLEZ” UNIVERSITY HOSPITAL
UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN
BODY COMPOSITION BY DUAL
X-ray absorptiometry in
Mexican schoolchildren
with or without obesity
INITIAL APPROACH
to first-time seizures
in pediatrics
HEALTH EFFECTS
due to exposure to
polycyclic aromatic
hydrocarbons from the
petroleum refining
industry
MEDICINA UNIVERSITARIA
HOW WE STUDY
and treat patients with
suspected thrombophilia
www.elsevier.es
medicina
universitaria
EDITORIAL COMMITTEE
General Director
Editor in Chief
Editor
Editor
Santos Guzmán López
Félix Ramón Cedillo Salazar
David Gómez Almaguer
Francisco Javier Bosques Padilla
Ariel Ernesto Arias Ramírez
Ottawa, Canadá
Alejandro Arroliga
Temple, EEUU
Norbert W. Brattig
Hamburgo, Alemania
María de los Ángeles Castro Corona
Monterrey, México
Technical Editor
Carlos Alberto Acosta Olivo
Ricardo Cerda Flores
Monterrey, NL
Technical Editor
Beatriz Elizabeth De la Fuente Cortez
Salvador Cruz Flores
St. Louis, EEUU
Technical Editor
Alfredo Arias Cruz
Assistant Editor
José Carlos Jaime Pérez
José A. González González
Monterrey, México
Oscar González Llano
Monterrey, México
Patricia de Gortari
EDITORIAL BOARD
Hugo Alberto Barrera Saldaña
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Francisco Forriol Campos
Alejandra García Quintanilla
Elvira Garza González
DF, México
Madrid, España
Mérida, México
Monterrey, México
René Raúl Drucker Colín
DF, México
Rubén Lisker Y.
DF, México
Pali Hungin
Ruy Pérez Tamayo
DF, México
José Luis Iglesias Benavides
Monterrey, México
Puebla, México
Patricia Ileana Joseph Bravo
Cuernavaca, México
Guillermo J. Ruiz Argüelles
Ralph Weissleder
Oliverio Welsh Lozano
Boston, EEUU
Monterrey, México
Susana Kofman Alfaro
David Kershenobich Stalnikowitz
Xavier López Karpovitch
DF, México
DF, México
Monterrey, México
Guillermo I. Pérez Pérez
Nueva York, EEUU
Mario Henry Rodríguez
Cuernavaca, México
Monterrey, México
Alejandro Ruiz Argüelles
Puebla, México
Guillermo J. Ruiz Delgado
Puebla, México
José Javier Sánchez
Madrid, España
Josep María Segur Vilalta
Eloy Cárdenas Estrada
Monterrey, México
Gregorio A. Sicard
Antonio Costilla Esquivel
Monterrey, México
Rolando Tijerina Menchaca
Lyuba Varticovski
Juan Pablo Figueroa Delgado
Monterrey, México
Claudia Elizalde Molina
Isaías Rodríguez Balderrama
Emma Bertha García Quintanilla
DF, México
Rochester, EEUU
Nahum Méndez Sánchez
English translation and style:
DF, México
Francisco López Jiménez
Laura E. Martínez de Villarreal
Biostatistics advisor:
Stockton-on-Tees, Reino Unido
Joseph Varon
Carlos E. Baena-Cagnani
Jordi Sierra Gil
Barcelona, España
St. Louis, EEUU
Monterrey, México
Maryland, EEUU
Houston, EEUU
Córdoba, Argentina
Barcelona, España
Medicina Universitaria, Volumen 16, número 64, julio-septiembre 2014, es una publicación trimestral de la Revista de Investigación y Ciencia de la Facultad de Medicina y Hospital
Universitario Dr. José E. González de la U.A.N.L. ISSN 1665-5796.
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medicina
universitaria
Contents
EDITORIAL
Volume 16
Issue 64
July-September 2014
105On body composition
C. Treviño-Garza
ORIGINAL ARTICLES
107Comparison of the efficacy and safety of 4 mg of ondansetron vs. 4 mg of
nalbuphine for the treatment of neuraxial morphine-induced pruritus
U. Cruz-Ferretti, H. A. Llanes-Garza, N. G. López-Cabrera, A. M. EspinosaGalindo, D. Palacios-Ríos, M. A. Cano-García, Y. N. Estrada-Solís
112Body composition by dual X-ray absorptiometry in Mexican schoolchildren
with or without obesity
M. E. de la O-Cavazos, C. Treviño-Garza, I. Rodríguez-Balderrama, J. Z. Villarreal-Pérez, R. Elizondo-Omaña, R. Montes de Oca-Luna, S. Sánchez-González, D. Cantú-Moreno, P. Rodríguez-Calderón, J. Argente-Oliver
117Sensitization to indoor aeroallergens in children who attended the Allergy
Service of the “Dr. José Eleuterio González” University Hospital of Monterrey,
Mexico
S. González-Díaz, A. Arias-Cruz, I. V. Yáñez-Pérez, L. Rangel-Garza, H. Hernández-Sánchez, A. Macías-Weinmann, C. Gallego-Corella
121Initial approach to first-time seizures in pediatrics
J. A. Infante-Cantú, M. A. Meza-Reséndiz, M. E. Chávez-Rede
125Prevalence of colonizing bacteria and their association with primary bacteremias in hemodialysis of a university hospital
C. G. Quiñonez-Olivas, I. M. Rivera-Morales, C. Sánchez-Martínez, H. R. IbarraSifuentes, R. O. Flores-Pérez, J. A. Cárdenas-de la Garza
scientific LETTERS
129Laryngeal amyloidosis: An uncommon cause of dysphonia
V. J. Villagómez-Ortiz, M. Villegas-González, J. L. Treviño-González, R. SantosLartigue, B. González-Andrade, N. Montemayor-Peña
133Surgical treatment of a pseudoaneurysm of the femoral artery secondary to a
gunshot wound. Clinical case report
M. A. Gómez-Álvarez, G. E. Muñoz-Maldonado, R. Salinas-Domínguez, M. Mercado-Flores, J. A. Tamez-del Bosque
medicina
universitaria
REVIEW ARTICLE
136Health effects due to exposure to polycyclic aromatic hydrocarbons from the
petroleum refining industry
M. T. Montaño-Soto, L. Garza-Ocañas
VOICES OF DOCTORS AND PATIENTS
141The new generation of residents
E. M. Treviño-Salinas
EXPERT’S CORNER: A PERSONAL APPROACH
143How we study and treat patients with suspected thrombophilia
G. J. Ruiz-Argüelles, G. J. Ruiz-Delgado
146Managing functional dyspepsia
Á. R. Flores-Rendón
Medicina Universitaria 2014;16(64):105-106
medicina
universitaria
www.elsevier.com.mx
Editorial
On body composition
The Greeks were the first to use the concept of “body composition” around the year 400 B.C. They believed events
and diseases had a natural origin. They thought human
beings consisted of the cosmos basic elements: fire, wind,
earth and water. However, it was not until the 20th Century
when major advances were made in the implementation of
different methods of body composition analysis. The studies
were evolving, going from merely experimental to studies of
impact in clinical practice.
In recent years, Mexico has been experiencing a nutrition
transition phenomenon, where an obesity epidemic coexists
with malnutrition.1 In clinical practice, the patient’s nutritional state can be evaluated using simple anthropometric
assessment methods. Body mass index (BMI) is the most utilized method for an obesity diagnosis. BMI has a moderately
high sensitivity to identify obesity in a child; however, it has
a poor correlation with total body fat, due to the considerable changes in fat mass during childhood.2 It is important to
stress that body composition changes are produced throughout childhood. Children, unlike adults, have a great variation in body composition (including fat and lean tissue),
due to maturation, growth, puberty and gender, thus decreasing the accuracy in body and/or abdominal fat estimation using these methods.3
Technological advances over the years have allowed the
development of multi-compartment models to measure
body composition. Examples include: Air displacement
plethysmography (Bod Pod®), hydrometry, isotonic solutions
prepared with deuterium oxide, dual-energy X-ray absorptiometry (DXA), in addition to computed tomography CT
scans and magnetic resonance imaging (MRI) scans. Body
composition analysis methods vary in precision, which is defined as the ability to approach the real value of a given
body component. A standard method is the one that is accepted as the closest representation of a true body composition, and used as a comparison standard for other
methods. The 4-compartment analysis method is considered
the gold standard for body composition study. Nevertheless,
it is not a practical measurement because it is expensive
and time-consuming. One important characteristic of body
composition techniques in children, in addition to its precision, is the fact that it is easy to perform on children of all
ages. Similarly, the method should be reproducible, available and safe.4 In this issue of Medicina Universitaria there is
a Mexican study comparing the composition between obese and non-obese children, illustrating our previous comment and proving that DXA is a highly precise technique,
quantifying the differences in lean and fat tissue, although
without proving any difference in mineral content.
Very few clinics have different methods available for body
composition measurement in clinical practice, and in recent
years, they have used Bod Pod® and DXA in clinical trials to
estimate body composition, with a relatively fast scan time,
good reproducibility and, in the case of DXA, minimum exposure to radiation.5
Having an additional clinical study, using a more appropriate and precise method to determine body composition
in children and teenagers, will help us have a better understanding of the key mechanisms which condition, mediate and
regulate the distribution and degree of adiposity. In addition,
it will give us, in clinical practice, a tool to evaluate the efficacy of interventionist strategies at a pediatric age.
References
1. Lobstein T, Baur L, Uauy R, IASO International Obesity Task Force. Obesity in children and Young people: a crisis in public
health. Obes Rev 2004;5(Suppl 1):4-104.
2. Ochiai H, Shirasawa T, Nishimura R, et al. Relationship of body
mass index to percent body fat and waist circumference among
schoolchildren in Japan the influence of gender and obesity: a
population-based cross-sectional study. BMC Public Health
2010;10:493-499.
3. Bauer J, Thornton J, Heymsfield S, et al. Dual-energy X-ray absorptiometry prediction of adipose tissue depots in children
and adolescents. Pediatr Res 2012;72:420-425.
* Corresponding author: Pediatrics Department, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Gonzalitos
Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. E-mail address: [email protected] (C. Treviño-Garza).
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados.
106
4. Sopher AB, Thornton JC, Wang J, et al. Measurement of percentage of body fat in 411 children and adolescents: a comparison
of dual-energy X-ray absorptiometry with a four-compartment
model. Pediatrics 2004;113:1285-1290.
5. Wells JC, Haroun D, Williams JE, et al. Evaluation of DXA against the four-component model of body composition in obese
children and adolescents aged 5-21 years. Int J Obes (Lond)
2010;34:649-655.
C. Treviño-Garza
C. Treviño-Garza*
Early Childhood Service, Pediatrics Departament,
“Dr. José Eleuterio González”
University Hospital, Universidad Autónoma
de Nuevo León, Monterrey, N.L., Mexico
medicina
universitaria
www.elsevier.com.mx
Original article
Comparison of the efficacy and safety of 4 mg of ondansetron vs. 4
mg of nalbuphine for the treatment of neuraxial morphineinduced pruritus
U. Cruz-Ferretti*, H. A. Llanes-Garza, N. G. López-Cabrera, A. M. Espinosa-Galindo, D.
Palacios-Ríos, M. A. Cano-García, Y. N. Estrada-Solís
Anesthesiology Service, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Monterrey, N.L., Mexico
Received: March 2014; Accepted: May 2014
KEYWORDS
Pruritus;
Ondansetron;
Morphine;
Nalbuphine; Neuraxial
analgesia; Mexico.
Abstract
Objective: To compare the efficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for
the treatment of neuraxial morphine-induced pruritus, in patients at the “Dr. José Eleuterio
González” University Hospital from September 2012 to August 2013.
Material and methods: A controlled, prospective, randomized study of 28 patients (14 per
group) receiving neuraxial morphine analgesia was conducted, which was registered and approved by the Ethics Committee of the Institution and patients agreed to participate in the study
under informed consent. The results were segmented and contrasted (according to drug) by
hypothesis testing; the association was determined by X2 with a 95% confidence interval (CI).
Results: Pruritus was effectively resolved in both groups and no significant difference was found
in the rest of the variables. An increase in the visual analogue scale (EVA) was observed at 6
and 12 hours for the ondansetron group, which was statistically significant (p≤0.05), however
both groups had an EVA of less than 3.
Conclusions: When comparing the efficacy and safety of ondansetron 4 mg vs. nalbuphine 4 mg
for the treatment of neuraxial morphine induced pruritus, the only significant difference found
was the mean EVA at 6 and 12 hours, favoring the ondansetron group. However, both groups
scored less than 3 on the EVA. Therefore, we consider that both treatments are effective and
safe in the treatment of pruritus caused by neuraxial morphine.
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos
los derechos reservados.
* Corresponding author: Anesthesiology Service, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Gonzalitos
Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (81) 1681 8404. E-mail address: [email protected] (U. CruzFerretti).
108
Introduction
Neuraxial administration of opioids provides excellent postoperative analgesia, however its use is associated with a
high incidence of side effects such as pruritus (itching), nausea, vomiting, urinary retention and respiratory depression.1-4
The term “pruritus” or “prurire” is an unpleasant sensation which causes the desire to scratch and varies in intensity. It is one of the most common side effects in epidural
and/or intrathecal administration of opiates with an incidence of approximately 60%, compared to 2%-10% of the patients treated systematically; thus, its incidence depends
on the route of administration. This symptom is common in
postpartum women. The most affected areas are those innervated by the trigeminal, probably due to their higher
number of opiate receptors in the spinal nucleus of the trigeminal nerve, causing patients to scratch their nose and
the upper part of the face. There are several chemical mediators responsible for pruritus (histamine, serotonin, cytokines, growth factors, prostaglandins, etc.).1-6,7
The cause of pruritus induced by the administration of
neuraxial opiates is uncertain; nevertheless there are 3
theories that may explain its origin. The 1st theory is associated with the release of peripheral histamine caused by
the administration of morphine; however, this theory has
not been proven because the antihistamines were ineffective in the treatment of pruritus caused by intrathecal morphine. The 2nd theory involves μ-opioid receptors responsible
for pain modulation and some side effects, especially pruritus, nausea and vomiting, in the central nervous system activated by morphine. This explains the antipruritic effects
of naloxone and nalbuphine, both μ-antagonists.2,3,8 A 3rd
theory is that pruritus induced by the administration of neuraxial opiates could be related to the excitatory effects of
opioids over nociceptive and non-nociceptive neurons in the
anterior and posterior horns. It has been reported that morphine can activate serotonin receptors due to an independent mechanism of the opioid receptors. Therefore, the
direct irritation of the serotonin type-3 receptors in the spinal cord, dorsal horn and bone marrow caused by the administration of morphine is possibly the mechanism of
pruritus.8
In light of the above, a great variety of medications has
been evaluated for the prevention and treatment of pruritus induced by opioids, including antihistamines, 5-hydroxytryptamine (5-HT3) antagonists, opioid receptor antagonists,
non-steroidal anti-inflammatory drugs, propofol and droperidol. None of them have had satisfactory results.1-3,9,10 Naloxone and nalbuphine are opioid antagonist drugs used for
this purpose and proven to be effective by different authors
as a therapeutic agent for the reversion of pruritus induced
by the neuraxial administration of opioids. Nalbuphine is an
agonist-antagonist opioid and its analgesic effect and probable antipruritic effect are mediated by its action in mu
and kappa receptors.4,10,11 These medications could play a
role in the treatment of pruritus, with a disadvantage,
however, because its preventive administration reduces its
analgesic effictiveness.3
Other medications used for the treatment of pruritus are the
5-HT3 receptor antagonists. Ondansetron, for example, which
has been successfully used in the treatment of neuraxial
U. Cruz-Ferretti et al
morphine-induced pruritus, because of its antipruritic
effect and its role in the nociception, contrary to the use of
opioid receptor antagonists.
The objective of our study was to compare the efficiency
and safety of 4 mg of nalbuphine vs. 4 mg of ondansetron,
for the treatment of neuraxial morphine-induced pruritus as
post-operative analgesic in patients programed for elective
surgery.
Material and methods
After the approval of the Ethics Committee and the Research Committee of the School of Medicine at the “Dr. José
Eleuterio González” University Hospital of Universidad Autónoma de Nuevo León (UANL, by its Spanish acronym), we
conducted a study from September 2012 to August 2013,
a controlled, prospective, comparative and randomized clinical trial with 28 patients programed for surgery under
neuraxial anesthesia and receiving epidural or subarachnoid
morphine analgesia. Patients who agreed to participate in
the trial had to sign an informed consent and meet the following criteria: ASA I and II patients, undergoing surgery
with neuraxial anesthesia and presenting pruritus secondary to the administration of epidural or subarachnoid morphine, either male and female between 18 and 50 years old, a
signed consent form, neurologically intact and able to assess pain using the visual analogue scale (EVA). We excluded
those patients with neurological alterations of the state of
consciousness, patients with a history of allergy to nalbuphine and ondansetron and local anesthetics, patients under 18
and older than 50 years of age, patients who did not accept
this type of administration of analgesia and patients with a
dermatological condition.
All patients were administered intravenous 10 mg of
metoclopramide and 50 mg of ranitidine intravenously as
pre-anesthetic medications. We monitored all patients with
a continuous electrocardiogram, pulse oximetry and noninvasive blood pressure every 5 minutes during the whole
procedure; they received oxygen at 5 L per minute through
a face mask. Subsequently, we applied a neuraxal block
(epidural, subarachnoid or both), once applied we administered local anesthetic and 100 mcg of morphine (subarachnoid or epidural) using the following formula (-0.01 * age +
1.85 mg). We assessed the presence of pruritus at 30 minutes
and 2, 6, 12 and 24 hours after morphine administration; the
patients who presented pruritus were divided into 2 groups:
group “O” (ondansetron) and group “N” (nalbuphine). We administered 4 mg of the corresponding drug to each group and
we registered the presence of pruritus, nausea, vomiting,
Ramsay sedation scale, blood pressure, respiratory frequency
and pain using the EVA scale from 0 to 10 (0 = no pain and 10
= intense pain) and the use of rescue medication.
The obtained results were gathered in a database developed using Microsoft Excel® and analyzed using IBM SPSS® Statistics v. 20.0. We obtained traditional descriptive statistics,
as well as observed frequencies in accordance with the
administered medication (ondansetron and nalbuphine)
through median and proportion hypothesis-testing, as the
case may be for each type of variable (quantitative and qualitative respectively) with a confidence interval (CI) of 95%.
Statistical association was determined using X2 with a 95% CI.
Comparison of the efficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for the treatment
of neuraxial morphine-induced pruritus
109
Table 1 Analysis of pruritus average by time.
Time
30 minutes
2 hours
6 hours
12 hours
24 hours
Average pruritus, O group
1.07
1.79
1.43
1.00
1.00
Average pruritus, N group
1.36
1.64
1.36
1.07
0.93
O group: ondansetron group; N group: nalbuphine.
N=28 patients (14 per group).
Source: Standardized instrument.
2.00
(blood pressure, Ramsay, respiratory frequency, nausea and
vomiting), we did not find a statistically significant difference (p>0.05) (Tables 2, 3 and 4).
1.00
Discussion
EVA O Average
s.
hr
24
s.
hr
12
s.
hr
6
hr
2
30
m
in
.
s.
0.00
EVA N Average
Figure 1 Analysis of visual analogue scale average by time.
Results
A total of 28 patients were studied, randomly distributed
into 2 groups of 14 patients each. The median age in the O
group was 26.9 and 28.7 for the N group. All of the patients
were female, programmed for a C-section. We performed
21 epidural blocks, 6 subarachnoid blocks and one combined subarachnoid-epidural technique.
In both groups mild pruritus (itching) occurred in 15 patients during the first 12 hours, moderate pruritus in 13
patients between the 2nd and 6th hour subsequent to the administration of morphine; this was resolved in all patients.
We did not find a significant difference between groups (Table 1).
The presence of pain was assessed according to the EVA, a
significant difference was found (p≤0.05) at 6 and 12 hours
in favor of the O group. The average score in the EVA pain
scale was less than 3, hence we did not administer any rescue medications (Fig. 1). When we analyzed the variables
Pruritus incidence subsequent to neuraxial morphine administration is approximately 60%, compared to 2%-10% of the
patients treated systematically. Thus, its incidence depends
on the route of administration. This symptom is common in
postpartum women. The most affected areas are those innervated by the trigeminal, probably due to their higher
number of opiate receptors in the spinal nucleus of the trigeminal nerve, causing patients to scratch their nose and
the upper part of the face. There are several chemical mediators responsible for pruritus (histamine, serotonin, cytokines, growth factors, prostaglandins, etc.).1-3,5-7
There is evidence that opioids and the serotonergic system interact closely in the central nervous system. One
example is ondansetron, a 5-HT3 antagonist with an antipruritic effect. In 1995 Fan reported that morphine can activate serotonin type-3 receptors in the spinal cord dorsal
horn and bone marrow and that could possibly be the mechanism causing pruritus.1-3,9,10,12,13
Since 1999 there have been studies comparing ondansetron’s
effectiveness in the treatment of epidural morphine-induced
pruritus, where its effectiveness has been demonstrated.8,12-15
In our study, pruritus occurred more frequently between 2 and
4 hours in both groups. These results are consistent with those
reported in medical literature.16 Pruritus caused by opioids
can be extremely difficult to manage and approximately 10%15% of the patients showed no response to naloxone.17
In our study, pruritus was effectively treated in both
groups and did not require the use of rescue medications.
We did not observe changes in the level of pain in the O
group; however, there was an increment in the EVA scale at
Table 2 Comparative analysis of Ramsey by time.
Time
30 minutes
2 hours
6 hours
12 hours
24 hours
Ramsey average, O group
1.93
2.07
2.00
2.07
2.00
Ramsey average, N group
2.00
2.14
2.29
1.93
1.93
O group: ondansetron group; N group: nalbuphine.
110
U. Cruz-Ferretti et al
Table 3 Comparative analysis of systolic blood pressure and diastolic blood average by time.
SBP 30
minutes
SBP 2
hours
SBP 6
hours
SBP 12
hours
SBP 24
hours
SBP 30
minutes
DB 2
hours
DB 6
hours
DB 12
hours
DB 24
hours
O group
125.14
121.57
122.14
120.57
118.57
76.36
73.71
73.23
72.57
71.14
N group
121.50
122.50
118.57
122.21
120.79
74.14
71.29
71.71
71.29
72.86
O group: ondansetron group; N group: nalbuphine; SBP: systolic blood pressure; DB: diastolic blood.
Table 4 Comparative analysis of heart rate and respiratory rate average by time.
HR 30
minutes
HR 2
hours
HR 6
hours
HR 12
hours
HR 24
hours
RR 30
minutes
RR 2
hours
RR 6
hours
RR 12
hours
RR 24
hours
O group
86
79.71
77.86
75.21
75.57
16.43
15.93
15.43
15.21
15.14
N group
75.71
74
74.57
73.21
71.64
14.79
15.00
15.36
14.93
15.07
O group: ondansetron group; N group: nalbuphine; HR: heart rate; RR: respiratory rate.
6 and 12 hours in the N group, probably because of its agonist-antagonist effect of the mu, kappa and delta receptors.
Nevertheless, both groups had an EVA score lower than 3.
We did not find differences in sedation levels in any of the
groups during the period of study.
The presence of nausea and vomiting is common after the
administration of opioids.18 Nausea occurs within the first 4
hours subsequent to the administration and vomiting occurs
right after this. High dosages of opioids can cause arteriolar
and venous dilatation, a decrease in peripheral vascular resistance and baroreceptors reflex inhibition, which can cause postural hypotension. Opioids cause dose-dependent
bradycardia, probably because of sympatholytic and parasympatholytic mechanisms. There were no statistically significant hemodynamic changes during the entire trial. Even
though opioids cause dose-dependent respiratory depression, there were no alterations in respiratory frequency in
the patients with nalbuphine.9
This study shows that nalbuphine was well-tolerated, only
displaying changes in the level of analgesia (EVA 3), which
did not require rescue medication, unlike ondansetron,
which did not display changes in analgesia levels and no side
effects were reported. However, both medications proved
to be safe and efficient for the treatment of neuraxial morphine-induced pruritus.
Conclusions
When comparing the efficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for the treatment of neuraxial
morphine-induced pruritus, the only significant difference
found was the mean EVA at 6 and 12 hours, favoring the ondansetron group. However, both groups had an EVA of less
than 3. Based on the obtained results we reject the null
hypothesis, which states that the administration of intravenous ondansetron at 4 mg is not as effective as the administration of nalbuphine at 4 mg in the treatment of neuraxial
morphine-induced pruritus.
Therefore, we consider that both treatments are effective and safe in the treatment of pruritus caused by neuraxial
morphine.
Conflicts of interest
The authors have no conflicts of interest to declare.
Funding
No financial support was provided.
References
1. Szarvas S, Harmon D, Murphy D. Neuroaxial opioid - induced
pruritus: a review, Journal de Clinical Anesthesia 2003;15:234239.
2. Accesed in June 2011. www.iqb.es
3. Kjellberg F, Tramèr MR. Control farmacológico del prurito inducido por los opiáceos: revisión sistemática cuantitativa de ensayo randomizado. European J Anaesthesiology 2001;18:346357.
4. Liao CC, Chang CS, Tseng CH, et al. Efficacy of intramuscular
nalbuphine versus diphenhydramine for the prevention of epidural morphine-induced pruritus after cesarean delivery, Chang
Gung Medical Journal 2011;34:172-178.
5. Lidstone V, Thorns A. Pruritus in cancer patients. Cancer Treat
Rev 2001;27:305-312.
6. Accesed in April 2011. www.fisterra.com
Comparison of the efficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for the treatment
of neuraxial morphine-induced pruritus
7. Accesed in July 2014. www.buscon.rae.es.
8. Charuluxananan S, Kyokong O, Somboonviboon W, et al. Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Thailand, Anesth
Analg 2003;96:1789-1793.
9. Hurley RW, Wu CL. Acute postoperative pain in Miller’s
Anaesthesia. 7th Edition. USA: Churchill Livingstone Ed.; 2010.
p. 2757-2770.
10. Kyokong O, Tamdee T, Charuluxananan S. Comparisson of the
efficacy of nalbuphine, tramadol, ondansetron and placebo in
the treatment of postanesthetic shivering after spinal anesthesia for cesarean delivery, Thailand, Asian Biomedicine
2007;1:189-194.
11. Kolm A, Ferraz AA, Módolo NS, et al. Prevention of itching after
spinal sufentanil: effects of droperidol, nalbuphine, ondansetron and the association of them. Rev Bras Anestesiol 2006;56:28-33.
12. Henderson SK, Cohen H. Nalbuphine augmentation of analgesia
and reversal of side effects following epidural hydromorphone.
EUA, Anesthesiology 1986;65:216-218.
111
13. Cavazzuti M, Porro CA, Barbieri A, et al. Brain and spinal cord
activity Turing propofol anaesthesia. England, Br J Anaesth
1991;66:490-495.
14. Somrat C, Oranuch K, Ketchada U, et al. Optimal dose of nalbuphine for treatment of intrathecal-morphine induced pruritus
after caesarean section. J Obstet Gynaecol Res (Japan)
1999;25:209-213.
15. Charuluxananan S, Kyokong O, Somboonviboon W, et al. Nalbuphine versus propofol for treatment of intrathecal morphineinduced pruritus alter cesarean delivery. Anesth Analg Thailand
2001;93:162-165.
16. Milner AR, Bogad DG. Intrathecal morphine for elective cesarean section. Anaesthesia EU 1996;51:871-873.
17. Wilder-Smith BA. Subhypnotic doses of propofol relieve pruritus
induced by epidural and intrathecal morphine. Anesthesiology
EU 1992;76:506.
18. Bromage PR, Camporesi EM, Durant PA, et al. Nonrespiratory
side effects of epidural morphine. Anesth Analg EU 1982;6:490.
medicina
universitaria
www.elsevier.com.mx
Original article
Body composition by dual X-ray absorptiometry in Mexican
schoolchildren with or without obesity
M. E. de la O-Cavazosa,*, C. Treviño-Garzaa, I. Rodríguez-Balderramaa, J. Z. VillarrealPérezb, R. Elizondo-Omañac, R. Montes de Oca-Lunac, S. Sánchez-Gonzáleza, D. CantúMorenoa, P. Rodríguez-Calderónd, J. Argente-Olivere
a
Pediatrics Department, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Endocrinology Service, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
b
c
School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N.L., Mexico
d
Children’s Medical Center S.A of C.V., Monterrey, N.L., Mexico
Pediatrics Department, School of Medicine, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco,
Madrid, Spain
e
Received: February 2014; Accepted: May 2014
KEYWORDS
Body composition;
Dual X-ray
absorptiometry;
Childhood obesity;
Body mass index; Fat
mass; Mexico.
Abstract
Objective: Apply dual X-ray absorptiometry (DXA) to determine the amount of fat mass, lean
mass, and bone mineral density in Mexican schoolchildren with and without obesity.
Material and methods: We performed an observational, analytical, comparative, cross-sectional
study of 80 Mexican schoolchildren who attended the Nutrition Clinic of the Pediatric Medical
Center in Monterrey, Mexico during the period of January to April 2005. Body mass index (BMI)
was determined to classify the participants according to the growth charts of the Centers for
Disease Control and Prevention. Two groups of 40 children each (with and without obesity) were
formed and DXA was carried out on each individual. Cronbach’s Alpha was used to determine
instrument reliability and the Kolmogorov-Smirnov test was used to test the normality of numerical variables. Means were compared using Student´s t test.
Results: Statistically significant differences were found in fat mass (p≤0.001) and lean mass
(p≤0.001), but not in bone mineral content (p=0.051) between both groups.
Conclusions: Differences exist in fat mass and lean mass in both groups, but not in bone mineral
content between both groups. A significant positive correlation was found between fat mass,
determined by DXA, and BMI in schoolchildren with and without obesity.
* Corresponding author: Pediatrics Department, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Gonzalitos
Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (+52 81) 8348 5421. E-mail address: [email protected] (M. E.
de la O-Cavazos).
Body composition by dual X-ray absorptiometry in Mexican schoolchildren with or without obesity
Introduction
The prevalence of obesity is increasing in children and adolescents in developed and developing countries and has become a health problem of great importance.1 According to
the National Health and Nutrition Survey, the combined national prevalence of obesity in 2012 in school-age children,
using the World Health Organization (WHO) criteria, was
34.4% (19.8% and 14.6%, respectively).2 Although the body
mass index (BMI) remains the most widely used method for
clinical diagnosis of obesity, it is not a measure of body composition because it only provides information about global
changes in the body, without specifying the components
that are specifically affected in situations of malnutrition
and/or obesity.3,4
There are several ways to indirectly measure adipose tissue. Among these are 2 kinds of impedance analyses: single
frequency and multi-frequency, which both calculate lean
body mass; however, their accuracy varies with hydration
and the presence of body fluids, although they have the advantage of being non-invasive and accessible. Likewise, there are other more sophisticated methods to assess body
composition: dual X-ray absorptiometry (DXA), computerized tomography (CT), and magnetic resonance imaging
(MRI), with the latter 2 being used for research purposes.
Although various methods are available, some have a number of disadvantages, such as low precision and a need for
the individual’s cooperation. This makes it necessary to find
an easy, reliable, and economical method that can be used
in professional clinical practice.
DXA is a method commonly used to determine bone mineral density, but it also accurately estimates fat mass and
fat-free mass.5,6 It is relatively fast and safe, providing high
accuracy and requiring little patient cooperation.7 Thus DXA
has some advantages over MRI, such as the relative ease of
access and simplicity of measurements.8,9
This highlights the importance of this study for clinical
application in children with and without obesity with respect to body composition by DXA, relating this to BMI and
associating the latter with metabolic abnormalities related
to excess adipose tissue.10 The purpose of this study is to use
DXA to determine whether there is any difference in the
content of fat mass, lean mass, and bone mineral density in
Mexican schoolchildren with and without obesity.
Material and methods
We developed an observational, cross-sectional, analytical
and comparative study. The participants were selected by
convenience and incidental sampling. The study included
80 Mexican children (6-12 years), who attended the Nutrition Clinic of the Child Medical Center in Monterrey, Mexico,
during the period of January to April 2005. All patients included in the study were sedentary and were divided into 2
groups: one group of 40 non-obese schoolchildren with a BMI
< 85th percentile only within the normal weight range and
another group of 40 obese students with a BMI ≥ 95th percentile. Female students who presented their menarche, both
male and female patients with onset of puberty, patients
taking corticosteroids and patients with conditions such as
Prader-Willi, Brader-Biedl, Ahlstrom, and Cohen syndrome
113
were excluded. The study was approved by the Research
Ethics Committee of the “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo
León (UANL, by its Spanish acronym). Patients older than 8
years provided assent and parents of all patients signed an
informed consent before entering their children in the study.11
Prior to the DXA study, a complete pediatric medical examination was performed and the patient’s weight was obtained with a scale with a 100 g precision (Health-O-Meter®,
McCook, IL, USA). Height was measured using a stadiometer
to the nearest 1 mm (SECA model 242, Hammer Steindam,
Hamburg, Germany). With these results, BMI (weight/
height2) was obtained.
Body composition analysis was performed by DXA (QDR,
Hologic Inc., Bedford, MA, USA), which provides measurements of the following variables: fat mass in grams, lean
mass in grams, and bone mineral content. Data were tabulated using Microsoft Excel®. Cronbach´s Alpha coefficient
was used to obtain the reliability of the instrument and the
Kolmogorov-Smirnov test was used to determine the normality in the numeric variables. Frequencies and percentages
are used for descriptive statistics, as well as measures of
central tendency (mean, median) and standard deviation
(SD). Finally, Student´s t test was used for comparison of
data.
Results
In this study, BMI was determined in 80 schoolchildren who
were classified as obese and non-obese, according to the
Centers for Disease Control and Prevention growth charts
and divided into 2 equal groups. Children of different ages
were included and the median age for both groups was determined; in the non-obese group the median was 9 years,
and in the obese group it was 8.5 years. The demographic
characteristics of the groups are shown in Table 1.
Regarding BMI, the girls in the non-obese group (n=16) had
a mean of 17.27 Kg/m2 and the boys (n=24) 18.45 Kg/m2; in
the obese group, girls (n=20) had a mean of 24.49 Kg/m2 and
boys (n=20) 25.14 Kg/m2. Fat mass in grams, lean mass in
grams, and bone mineral content were determined in both
groups, obtaining the mean, median, SD and p value for the
different parts of the body, and as a whole (Table 2). With
regard to the analysis of fat mass in grams in the different
parts of the body, the non-obese group showed that the
greatest amount was located in the trunk ( = 2,958 ± 1,502
g), while the lowest value was found in the left arm ( =
504 ± 288 g). In the group with obesity, for fat mass in grams
according to the different parts of the body, the trunk was
also the area with the highest value ( = 7,297 ± 2,376 g),
with the head scoring the lowest ( = 857 ± 122 g).
In the non-obese group, lean mass in grams was greater in
the trunk ( = 10,555 ± 2,546 g) and lowest in the left arm
( = 1,138 ± 333 g). When lean mass in grams was determined in different areas of the body, in the obese group it was
observed that the trunk had the greatest amount (
=
12,809 ± 2,804 g) and the left arm the lowest ( = 1,279 ±
351 g).
Analysis of bone mineral content in grams in the non-obese group showed a greater amount in the head ( = 319.4 ±
114
M. E. de la O-Cavazos et al
Table 1 Distribution by age and gender of children in groups with and without obesity.
Group with obesity (n=40)
Group without obesity (n=40)
Gender
Gender
Female
Male
Female
Male
Age, years
Frequency (%)
Frequency (%)
Frequency (%)
Frequency (%)
6
2 (2.5)
4 (5)
0 (0)
6 (7.5)
7
3 (3.7)
2 (2.5)
2 (2.5)
3 (3.7)
8
6 (7.5)
3 (3.7)
5 (6.2)
1 (1.2)
9
6 (7.5)
3 (3.7)
7 (8.7)
4 (5)
10
1 (1.3)
2 (2.5)
0 (0)
7 (8.7)
11
2 (2.5)
3 (3.7)
1 (1.2)
2 (2.5)
12
0 (0)
3 (3.7)
1 (1.2)
1 (1.2)
Total
20 (25)
20 (25)
16 (20)
24 (30)
44.1 g) and the lowest in the left arm ( = 52.9 ± 21.5 g). In
the obese group, the bone mineral content in grams was
greatest in the head ( = 309.0 ± 51.7 g) with the lowest
content in the left arm ( = 64.1 ± 17.0 g). Moreover, body
composition as a percentage of total fat mass, lean mass
and bone mineral content were determined in both groups.
When comparing the means of both groups, significant differences in fat mass and lean mass were found. In the obese
group a mean bone mineral content of 1,094 was found and
in the non-obese group of 979, which, although it was not
statistically significant (p=0.051) showed a trend toward increased bone mineral content in obese children, which is
probably due to dietary and environmental factors (Table
3). A significant positive correlation was found between BMI
and total fat mass in grams calculated by DXA (Table 4).
Discussion
Although a consensus on the clinical parameter with the
most discriminative ability to detect and quantify excess
body fat has not been reached, most agree that the most
suitable method for estimating body fat should be based on
anthropometric measures because of its accessibility, simplicity and reproducibility, harmlessness, and low cost. The
BMI is an indicator of body fat, but the relationship between
BMI and percentage of body fat varies among individuals.
Therefore, it is important to distinguish whether the excess
weight is truly due to fat or muscle since we must not forget
that children who are overweight but do not have excess fat
do not have an increased health risk.12-15
DXA is becoming an extremely useful tool for assessing
changes in bone mass, muscle mass, and especially fat mass
not only in adults but children and adolescents.
Haroun et al.16 analyzed body composition in obese and
non-obese Ukrainian children analyzing lean mass. Their
study showed that lean mass is different in obese and nonobese children. Body water and mineral content are higher
in obese children. These results are consistent with our data
regarding the analysis of lean mass, where we also found
statistically significant differences between the 2 groups.
Again, as with fat mass, the trunk had the greatest percentage of lean body mass in both groups. Likewise, boys had
the highest amount of lean mass.
The trunk was the area where the greatest amount of fat
was found in both groups; this amount showed statistically
significant differences between children with and without
obesity. These results are consistent with data published in
medical literature in studies using the same method to assess body composition.17 We found that boys in both groups
showed more body fat than girls, while female patients with
obesity often have early, accelerated and rapidly progressive puberties compared to their non-obese peers, leading to
an earlier presentation of pubertal changes in body composition, the group of female patients in our study had not yet
presented pubertal changes. The distribution of fat mass is
clinically important because these deposits in the thoracoabdominal region could be predictive in children with diseases such as diabetes and hyperlipidemia, among
others.
We found a positive and statistically significant correlation between BMI and fat mass in both groups of Mexican
schoolchildren, making it possible to conclude that this index can also be applied to the Mexican population. The results of our study show that BMI is an indicator of adiposity
and it correlates with fat mass determined by DXA. These
results are consistent with those described in other publications. Pietrobelli et al.18 found a correlation between BMI
and percentage of body fat measured by DXA in ranges of
0.85 and 0.89 for children 5 to 19 years of age.
Leonard et al.19 mentioned in their research that obesity
during childhood and adolescence is associated with increased bone density and body mass. It is also known that estrogen plays a role in female patients who have already
submitted their menarche and likewise in pubertal male
patients; aromatase converts testosterone to estrogen, and
these play an important role in bone mass gain. However,
this was not the case in our study as none of the patients
Body composition by dual X-ray absorptiometry in Mexican schoolchildren with or without obesity
115
Table 2 Differences in body composition in children with and without obesity in Monterrey, Mexico.
Group without obesity (n=40)
X
SD
Median
Group with obesity (n=40)
X
SD
Median
p
Fat mass (g) by area
Left arm
504
288
448
1,296
545
1,124
<0.0001
Right arm
519
320
447
1,366
604
1,184
<0.0001
Trunk
2,958
1,502
2,535
7,297
2,376
7,046
<0.0001
Left leg
1,725
866
1,681
3,367
964
3,25
<0.0001
Right leg
1,733
841
1,678
3.43
993
3,204
<0.0001
Head
695
68
679
857
122
849
<0.0001
Total
8,134
3,759
7,267
17,613
5,331
16,669
<0.0001
Left arm
1,138
333
1,109
351
1,177
0.0692
Lean mass (g) by area
1,279
Right arm
1,211
357
1,226
1,377
406
1,288
0.0559
Trunk
10,555
2,546
10,545
12,809
2,804
12,453
0.0003
Left leg
3,791
975
3,86
4,298
1,009
4,078
0.025
Right leg
3,797
972
3,894
4,356
1,043
4,163
0.0153
Head
2,681
258
2,628
3,154
357
3,152
<0.0001
Total
23,173
5,262
23,678
27,274
5,724
26,525
0.0013
Left arm
52.9
21.5
49.2
64.1
17
63.6
0.0022
Right arm
55.7
23.9
53.8
68.2
20.3
64.6
0.0138
Bone mineral content (g) by area
Trunk
215.2
62.4
208
247.2
64
236.6
0.0025
Left leg
169.2
63.7
164.5
201.3
65.8
188.4
0.0296
Right leg
166.8
62.5
157.3
204.7
68.3
195.4
0.0115
Head
319.4
44.1
324.7
309
51.7
300.2
<0.0001
Total
979.3
259.7
931.3
1,094.5
261.3
1,041.4
0.0515
SD: standard deviation.
had onset of puberty. In our study, the determination of
bone mineral content showed no statistically significant difference between the 2 groups. These data do not agree
with what is described in medical literature,20-22 although it
is probably due to dietary and environmental factors as described by Jurimae23 in Estonia, who conducted a study on
the factors affecting bone density and bone mineral content. These factors include age, since 90% of bone mass is
reached at age 18 for women and 22 years for men, making
those the best ages for evaluation; nutritional status, which
should be taken into account since obese patients often
have accelerated bone mineralization, with advanced bone
age and size above the familiar; and physical activity, with
the latter playing an important role in bone density development. Likewise, there are other rare diseases that affect
bone mineral density, namely Turner syndrome, Noonan syndrome, Klinefelter syndrome, Kallman syndrome and others
associated with hypogonadism, congenital adrenal hyperplasia, Cushing’s endogenous syndrome, rickets, renal tubular acidosis, deletions of 22q11, hypo and hyperthyroidism
disorders, hormone deficiency and growth resistance,
parathyroid disorders, kidney disorders, inactivating and activating mutations of GNAS, use of loop diuretics, bone dysplasias and rheumatic diseases.
By using DXA, we were able to assess its application in
children. One of its main advantages is its low radiation
dose, plus the pediatric patient is at an age to cooperate
comfortably during the procedure, therefore there is no
need for sedation and it is very quick. It would be desirable
in the future to expand the sample size and classify patients
by pubertal stage to establish baseline reference values. It
is important to continue studies involving DXA, so that it
becomes a useful tool for assessing changes in fat mass,
lean mass, and bone mineral content in childhood, to unify
reference values.
116
M. E. de la O-Cavazos et al
Table 3 Comparison of body composition between 2 groups of children in Monterrey, Mexico.
Group without obesity
X ± SD
Body composition (g)
Total fat mass
Total lean mass
Total bone mineral content
Group with obesity
X ± SD
p
8,134 ± 3,886 (24.2%)*
17,613 ± 5,605 (37.8%)*
0.001
23,173 ± 5,441 (72.8 %)*
27,274 ± 5,970 (59.8%)*
0.001
979 ± 278 (3.0%)*
1,094 ± 287 (2.4%)*
0.051
SD: standard deviation.
* Total percentage of body composition.
Table 4 Correlation between BMI and total fat mass
calculated by dual X-ray absorptiometry in both groups.
Group
TFM/BMI
R
p
Without obesity (n=40)
0.92
<0.001
With obesity (n=40)
0.86
<0.001
TFM: total fat mass; BMI: body mass index.
Funding
References
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long-term risk of obesity: evidence from 2 randomized controlled trials. Am J Clin Nutr 2010;92:1133–1144.
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3. Freedman DS, Wang J, Maynard LM, et al. Relation of BMI to fat
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the four-component model of body composition in obese children and adolescents aged 5 to 21 years. Int J Obes (Lond)
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8. Gately PJ, Radley D, Cooke CB, et al. Comparison of body composition methods in overweight and obese children. J Appl Physiol 2003;95:2039–2046.
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model. Pediatrics 2004;113:1285-1290.
11. Ize LL. Aspectos éticos de la atención nutricia. In: Casanueva E,
Kaufer HM, Pérez LA, et al (eds). Nutriología Médica. 2a Ed. México: Panamericana; 2001. p. 350-352.
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13. Calarge CA, Xie D, Fiedorowicz JG, et al. Rate of weight gain
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medicina
universitaria
www.elsevier.com.mx
Original article
Sensitization to indoor aeroallergens in children who attended the
Allergy Service of the “Dr. José Eleuterio González” University
Hospital of Monterrey, Mexico
S. González-Díaz, A. Arias-Cruz*, I. V. Yáñez-Pérez, L. Rangel-Garza, H. HernándezSánchez, A. Macías-Weinmann, C. Gallego-Corella
Regional Center of Allergy and Clinical Immunology (CRAIC), “Dr. José Eleuterio González” University Hospital, Universidad
Autónoma de Nuevo León, Monterrey, N.L., Mexico
Received: February 2014; Accepted: June 2014
KEYWORDS
Sensitization;
Aeroallergen; Indoor;
Pediatric; Mexico.
Abstract
Background: Indoor aeroallergens are the main cause of sensitization in children and represent
a risk factor for the development of allergic diseases.
Objective: Identify the major indoor aeroallergens most often sensitized to pediatric patients treated at the Allergy Service at the “Dr. José Eleuterio González” University Hospital of Monterrey
Methods: We performed an observational and descriptive study where we reviewed reports of
positive skin tests to the following common indoor aeroallergens: Dermatophagoides farinae (D.
farinae), Dermatophagoides pteronyssinus (D. pteronyssinus), Canis familiaris (C. familiaris),
Felis domesticus (F. domesticus), Blattella germanica (B. germanica) and Periplaneta americana (P. americana), found in patients under 16 years with symptoms of allergy, during the period
of 2011-2012.
Results: We performed 439 skin tests to aeroallergens in pediatric patients. Of these, 57.6%
were male and 42.4% were female. Mean age was 6.3 years. The age groups were under 3 years:
17.8%, 3-5 years: 35%, 6-12 years: 36%, and 13-16 years: 11.2%. The main diagnoses were: allergic rhinitis (71.8%), asthma (16.6%), and atopic dermatitis (4.3%). In 57.9% of the cases, they
had at least one positive skin test to any aeroallergen. The rate of sensitization to specific aeroallergens was: D. Pteronyssinus 49.0%, D. farinae 44.6%, B. germanica 13.9%, P. Americana
10.9%, F. domesticus 10.7%, and C. familiaris 5.9%.
Conclusion: Indoor aeroallergen sensitization can occur early in life, although it was more frequent in the preschooler and elementary school group. Dust house mites were the most commom cause of allergic sensitization.
* Corresponding author: Regional Center of Allergy and Clinical Immunology (CRAIC), “Dr. José Eleuterio González” University Hospital.
Francisco I. Madero and Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (81) 8346 2515. Fax: (81) 8347
6798. E-mail address: [email protected] (A. Arias-Cruz).
118
Introduction
The prevalence of organ-specific allergic diseases, such as
allergic rhinitis, asthma and atopic dermatitis is on the rise
worldwide.1 There is substantial evidence associating allergic sensitization and a hike in allergy and asthma morbidity
to early exposure to environmental allergens.2 Atopic children usually begin with monosensitization (sensitization to a
single allergen), however, with time they begin sensitizing
to other allergens.3 Identification during the early stages of
life is required in order to start a specific treatment and be
able to modify the allergic disease’s natural history. Skin
tests are used to assess IgE-mediated hypersensitivity, and
confirm clinical sensitivity induced by allergens and other
agents.4,5
The objective of this study was to identify the most frequent indoor aeroallergens which cause sensitization in children who attend the allergy outpatient clinic of “Dr. José
Eleuterio González” University Hospital of the Universidad
Autónoma de Nuevo León (UANL, by its Spanish acronym).
S. González-Díaz et al
Table 1 Demographic data.
N (%)
Skin prick tests in pediatric patients
439 (100)
Gender
Male
Female
253 (57.6)
186 (42.4)
Age groups
Less than 3 years
3 to 5 years
6 to 12 years
13 to 16 years
78 (17.8)
154 (35)
158 (36)
49 (11.2)
Device used for skin tests
Duotip-Test®
Multi-Test®
182 (41.5)
257 (58.5)
Diagnosis
Allergic rhinitis
Asthma
Atopic dermatitis
A combination of the above
315 (71.8)
73 (16.6)
19 (4.3)
32 (7.3)
Methods
We conducted an observational and descriptive study. We
reviewed the results of the skin tests for the most common
indoor aeroallergens on children under 16 who went for a
consult at the Allergy and Immunology Regional Center Clinic of “Dr. José Eleuterio González” University Hospital of
the UANL, Mexico between 2011 and 2012.
We collected demographic data: age, gender, clinical
diagnosis and skin test results for 6 common indoor aeroallergens: Dermatophagoides farinae (D. farinae), Dermatophagoides pteronyssinus (D. pteronyssinus), Canis familiaris (C.
familiaris), Felis domesticus (F. domesticus), Blattella germanica (B. germanica) and Periplaneta americana (P. americana).
Skin prick tests were performed using commercial allergen
extracts, Duotip-Test® (Lincoln Diagnostics, Decatur, IL) or
Multi-Test® (Lincoln Diagnostics, Decatur, IL), as well as a
negative control with a saline solution of 0.9% and a positive
one with 10 mg/mL of histamine. We considered a positive test that which caused a ≥ 3 mm wheal compared to the
negative control.
The collected data was analyzed using Statistical Product
and Service Solutions 17 (SPSS® Statistics v. 17.0). We evaluated nominal and ordinal variables, and determined frequencies and percentages.
Results
We evaluated a total of 439 skin tests to indoor aeroallergens in children under 16. The 57.6% of children were male
and 42.4% female (Table 1). The most utilized device for
skin tests was Multi-Test® (58.5%). On the other hand, Duotip-Test® was used in 41.5% of the cases. There were no reports of complications with either device.
The clinical diagnoses included: allergic rhinitis (71.8%),
asthma (16.6%), and atopic dermatitis (4.3%). The 7.3% of
children had 2 or more of these allergic diseases.
Two hundred and fifty-four of studied patients (57.9%)
showed sensitization to at least one of the 6 tested aeroallergens. The main indoor aeroallergens causing sensitization in
children included D. pteronyssinus (49%), D. farinae (44.6%)
and B. germanica (13.9%) (Table 2).
The rate of specific sensitization per age group was as follows: 38% in children under 3 years, 51.3% in children between 3 and 5 years, 69% in children between 6 and 12 years
and 73% in children between 13 and 16 years of age (Fig. 1).
The older the child, the more frequent the sensitization
to indoor aeroallergens. Sensitization to dust house mites
-mainly D. pteronyssinus- occurred in all age groups. Cockroach sensitization displayed a directly proportional relationship with age, with a greater prevalence to B. germanica
in children over 6 years of age. Sensitization rate for C. familiaris displayed a higher proportion in children under 3
years with 27%, decreasing as children get older, reaching
3% in the 13 to 16 group.
Discussion
Indoor aeroallergen sensitization increases the risk of developing allergic diseases, including asthma, allergic rhinitis
and atopic dermatitis.6 Different studies conducted in pediatric populations, as well as in adults who suffered from
allergies, have shown that as time passes monosensitization
leads to allergenic polysensitization, which constitutes a
characteristic of the natural history of atopia.7,8 In our study, the rate of indoor allergen sensitization was 57.7%, similar to the results obtained in a study conducted by Sheehan
et al. in a pediatric population in Boston, where they reported a sensitization of 51.3% for at least one indoor allergen,2
whereas in the general population sensitization to indoor
allergens occurs up 30% of people.9
D. pteronyssinus and D. farinae were the most prevalent
indoor aeroallergens as a cause of sensitization in the children in our study. In a study conducted by Kim et al. in a
pediatric population in Korea, they found a prevalence of
sensitization to D. pteronyssinus of 32.1% and 42.7%, and to
Sensitization to indoor aeroallergens in children who attended the Allergy Service of the
“Dr. José Eleuterio González” University Hospital of Monterrey, Mexico
100
Table 2 Sensitization to indoor aeroallergens.
Patients with at least one positive skin test
Positive aeroallergens
Dermatophagoides pteronyssinus
Dermatophagoides farinae Blattella germanica Periplaneta americana
Felis domesticus Canis familiaris
119
90
N (%)
80
254 (57.9)
70
60
215 (49.0)
196 (44.6)
61 (13.9)
48 (10.9)
47 (10.7)
26 (5.9)
50
40
30
20
10
0
D. farinae of 32.4% and 41.9%, in children between 6 and 7
years of age and between 12 and 13 years of age, respectively.10 On the other hand, the prevalence of sensitization to
dust house mites had been reported up to 27.5% of people in
the general population in the US.11 This shows that indoor
allergen sensitization prevalence is greater in the studies
where a pediatric population is included and in those studies where the patients are assessed by an allergy specialist.
Sensitization to cockroaches was at 13.9% for B. germanica and of 10.9% for P. Americana. Calabria et al. reported a
general sensitization to cockroaches of 12.5% in children
with rhinitis.12 In our study, sensitization to cat was 5.9%,
similar to the data found in a cohort study from birth to 4
years of age, with a sensitization of 5.1%.13 On the other
hand, Espinoza et al. found sensitization to cat at 10%, in
children up to 4 years old,14 which differs from our study,
where sensitization to cat in children up to 5 years old was
just 3.8%.
Sensitization to aeroallergens can occur in the early stages of life, increasing as the person ages, in many cases
going through monosensitization to polysensitization.15 It is
possible to see this transition from monosensitization to polysensitization in pre-school and school-aged children.
In a meta-analysis published by Goldhahn et al., they
found a rise in aeroallergen sensitization from 14.2% to
21.6% in patients from 7 to 23 years of age.16 Similar data
can be found in a study of children conducted in Turkey
where the prevalence in children from 2 to 6 years of age
was at 16.1% increasing up to 55.1% in patients 12-18 years
of age.17 In pediatric population, the prevalence of sensitization to dust mites, cockroaches, dog and cat appears to
be higher in older patients.2 Sensitization to dust mites, and
to a lesser degree to pollens seems to have a “triggering”
effect in the developing of polysensitization, due to the large number of children who are initially monosensitized to
mites.18 A recent preliminary study suggests that a defect in
the function of regulatory T cells can explain the tendency
to develop polysensitization in this population, because
children with persistent monosensitization produce a larger
amount of interleukin 10 and interferon gamma than the
children who develop polysensitization.19
In the pediatric population that goes to see the doctor at
the Allergy Outpatient Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL, indoor aeroallergen
< 3 years
3 to 5 years
6 to 12 years 13 to 16 years
D. farinae
D. pteronyssinus
D. americana
D. germanica
D. domesticus
D. familiaris
Figure 1 Distribution of sensitization to aeroallergens by age
group.
sensitization is around 50% and D. pteronyssinus and D. farinae are the main involved allergens. In the atopic population, frequency of sensitization directly increases with the
patient’s age; however it may be present from the early
stages of life. Early detection is recommended using skin
tests on all children under suspicion of allergy, in order to
begin a timely treatment and modify the natural history of
the allergic disease.
Funding
References
1. Gupta R, Sheikh A, Strachan DP, et al. Time trends in allergic
disorders in the UK. Thorax 2007;62:91–96.
2. Sheehan WJ, Rangsithienchai PA, Baxi SN, et al. Age-specific
prevalence of outdoor and indoor aeroallergen sensitization in
Boston. Clin Pediatr 2010;49:579-585.
3. Melioli G, Marcomini L, Agazzi A, et al. The IgE repertoire in
children and adolescents resolved al component level: a crosssectional Study. Pediatr Allergy Immunol 2012;23:433-440.
4. Bernstein IL, Li JT, Bernstein DI, et al. Allergy Diagnostic Testing: An Updated Practice Parameter. Ann Allergy Asthma Immunol 2008;100:S1-148.
5. Sharma HP, Hansel NN, Matsui E, et al. Indoor environmental
influences on children’s asthma. Pediatr Clin North Am
2007;54:103-120.
6. McHugh BM, MacGinnitie AJ. Indoor allergen sensitization and
the risk of asthma and eczema in children in Pittsburgh. Allergy
Asthma Proc 2011;32:372-376.
7. Baatenburg de Jong A, Dikkeschel LD, Brand PL. Sensitization
patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polisensitized
children. Pediatr Allergy Immunol 2011;22:166-171.
120
8. Canonica GW, Bousquet J, Mullol J, et al. A survey of the burden of allergic rhinitis in Europe. Allergy. 2007;62(suppl 85):1725.
9. Calabria CW, Dice JP, Hagan LL. Prevalence of positive skin test
responses to 53 allergens in patients with rhinitis symptoms.
Allergy Asthma Proc 2007;28:442-448.
10. Kim J, Hahm MI, Lee SY, et al. Sensitization to aeroallergens in
Korean children: a population-based study in 2010. J Korean
Med Sci 2011;26:1165-1172.
11. Arbes SJ Jr, Gergen PJ, Elliott L, et al. Prevalences of positive
skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2005;116:377-383.
12. Calabria CW, Dice J. Aeroallergen sensitization rates in military
children with rhinitis symptoms. Ann Allergy Asthma Immunol
2007;99:161-169.
13. Arshad SH, Tariq SM, Matthews S, et al. Sensitization to common allergens and its association with allergic disorders at age
4 years: a whole population birth cohort study. Pediatrics
2001;108:E33.
S. González-Díaz et al
14. Espinosa SE, Meza MR, Orozco S, et al. Sensibilización temprana
a aeroalergenos en una población pediátrica mexicana. Alergia
e Inmunol Pediatr 1999;8:165-169.
15. Silvestri M, Oddera S, Crimi P, et al. Frequency and specific sensitization to inhalant allergens within nuclear families of children with asthma and/or rhinitis. Ann Allergy Asthma Immunol
1997;79:512-516.
16. Goldhahn K, Bockelbrink A, Nocon M, et al. Sex-specific differences in allergic sensitization to house dust mites: a metaanalysis. Ann Allergy Asthma Immunol 2009;102:487-494.
17. Şahiner UM, Civelek E, Yavuz ST, et al. Skin prick testing to aeroallergen extracts: what is the optimal panel in children and
adolescents in Turkey? Int Arch Allergy Immunol 2012;157:391398.
18. Cipriandi G, Melioli G, Passalacqua G, et al. Immunotherapy in
polysensitized patients: new chances for the allergist? Ann
Allergy Asthma Immunol 2012;109:392-394.
19. Prigione I, Morandi F, Tosca MA, et al. Interferon-gamma and
IL-10 may protect from allergy polysensibilization in children:
preliminary evidence. Allergy 2010;65:740-742.
medicina
universitaria
www.elsevier.com.mx
Original article
Initial approach to first-time seizures in pediatrics
J. A. Infante-Cantú, M. A. Meza-Reséndiz*, M. E. Chávez-Rede
Pediatrics Department, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Received: February 2014; Accepted: June 2014
KEYWORDS
Unprovoked seizures;
Electroencephalography; Mexico.
Abstract
Objective: Prove that conducting complementary studies at laboratories and imaging studies
are unnecessary in first-time unprovoked seizures, since there is no change in the evolution and
prognosis of the disease, as well as the study of our population, the incidence rate and the proportion of our patients that have been studied and given maintenance treatment, so it can be
determined whether or not our population should follow the suggestions of the American
Academy of Pediatrics and the Spanish Pediatric Association.
Methods: An observational study, including patients diagnosed with first-time unprovoked seizures. They were followed up on by the emergency department and information was collected
from their clinical history and compared with the results of the different studies between patients that suffered just one seizure and the ones that had recurrent seizures.
Results: Thirty one patients were included, 14 males and 17 females. The average age was 5.5
years old. The 100% of patients were studied, and the groups were compared. The significant
study was the electroencephalogram (EEG) with a p=0.02 (significance p<0.05), incidence of
41%.
Conclusions: The study and diagnosis of first-time unprovoked seizures is based on clinical manifestations. The EEG is important in the study and classification of unprovoked seizures. Our
population has an incidence and recurrence rate similar to that in the bibliography, and for that
reason, this study suggests that the diagnostic and therapeutic guidelines of the American Academy of Pediatrics and the Spanish Pediatric Association should be followed.
* Corresponding author: Pediatrics Department, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Dr. Eduardo
Aguirre Pequeño Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (81) 1041 1400. E-mail address: mayela87@hotmail.
com (M. A. Meza-Reséndiz).
122
Introduction
About 5% of the patients who arrive at the emergency room
are admitted with a seizure diagnosis.1 Management of these patients is determined by the first-contact pediatrician;
they decide whether or not the patient gets exams/tests, is
admitted and begins treatment.1 There is no standardized
algorithm for the initial assessment of a patient who had a
seizure for the first time, therefore a thorough case history
and physical examination are required in order to determine additional lab and neuroimaging testing. 2 Academic
groups like the American and European Pediatrics Association suggest that neither additional testing or medical admittance are necessary for patients who had generalized
unprovoked seizures.3
Currently we do not have studies describing our population; therefore we must follow the recommendations and
guidelines given by these academic groups; for this reason
we are conducting this research. Our main objective is to
prove there is no need for additional lab and neuroimaging
testing for patients who had generalized unprovoked seizures because it does not modify management, evolution or
prognosis. Moreover, as specific objectives we will study the
following: first-time generalized unprovoked seizure incidence at the “Dr. José Eleuterio González” University Hospital, percentage of patients who get additional procedures
and/or additional studies, costs and length of hospital stays,
the number of patients discharged with anti-seizure
treatment and the most utilized anti-seizure in an acute
event and subsequent to the event.
Methods
We designed an observational, descriptive, logitudinal, nonblind, prospective study.
We included in our population, patients of the “Dr. José
Eleuterio González” University Hospital. We calculated the
sample size using the finite population formula, with a result of 25 patients who had a first-time unprovoked seizure
incidence in order to have significant results. This study was
conducted over a period of 2 years; therefore we were able
to include a total of 31 patients. We followed the patients
during their medical visit and during their first followup appointment within the first month. The study and
treatment was determined by the on-call doctor in the Pediatric Emergency Room at the University Hospital. We as
researchers did not intervene in the decision making process. We obtained the information from their clinical files,
gathering the following variables: age, gender, family history, perinatal history, use and type of anti-seizure in the
acute event and subsequent to it and if they had studies
performed, like a complete blood count (CBC), basic metabolic panel (BMP), lumbar puncture, electroencephalogram
(EEG), computed tomography (CT) and magnetic resonance
(MRI). The variables were compiled in a database created
using Microsoft Excel®, later to be analyzed using statistical
software SPSS® Statistics v. 20.0. Continuous variables will
be expressed in median and standard deviation (SD) or ranges, on the other hand categorical variables will be described in percentages.
J. A. Infante-Cantú et al
We included patients ranging from 6 months to 16 years
old, with a first-time seizure diagnosis, generalized, unprovoked, about 5 minutes long, without focalization data after
the event, with a normal neurological exam. We excluded
patients with provoked seizures, history of previous seizures, patients with an epilepsy diagnosis, psychomotor development alterations, a previous brain injury, intoxication,
gastrointestinal problems, vomiting and diarrhea, patients
with dehydration data or central nervous system infection
data and patients with an abnormal neurological exploration.
We divided the patients into 2 groups, patients who displayed recurrence in one group, and those who did not in
the other group. We compared their lab and clinical tests’
results to verify that they were not anticipating immediate
seizure evolution and/or complications. We defined immediate complications to the recurrence of seizures within the
first month. We also divided the patients who received
treatment from those who did not, in order to assess recurrence.
Results
Our sample size required a minimum of 25 patients; however, we managed to include 31 patients who met the inclusion criteria. We had 14 males and 17 females, with a
median age of 5.5 years of age. Out of the 31 patients, there were 7 (22.6%) with a family history and 24 (77.4%)
without, 3 (9.7%) had perinatal history and 28 (90.3%) did
not.
We studied 31 patients as follows: We performed a lumbar
puncture in 5 of them (0 abnormalities reported), 24 BMP (0
alterations), 26 CBC (2 altered results) and 24 neuroimaging
scans (CT and MRI) with one altered result which was reported as a finding without being a cause of seizure. We performed an EEG in all 31 of the patients of which 14 were
reported abnormal.
We compared the different test results from patients who
experienced a recurrent episode to those patients who did
not experience one, to verify if the results of the studies
change or predict recurrences; of these the only one who
showed significant results was p=0.02 the EEG (Table 1).
Out of the 31 patients who went to the emergency room,
we began anticonvulsant treatment in 19 patients. Twelve
patients were discharged conservatively, without anti-seizure treatment. Out of the 19 patients, 14 were given phenytoin, and 5 patients were given valproic acid.
We compared seizure recurrence in patients discharged
with treatment to those patients discharged without it,
which showed a non-significant result with p=0.69, with an
Odds Ratio (OR) of 0.55 and a confidence interval (CI) of
0.12-2.49, showing that the indication of chronic treatment
is not a factor in protecting the patient against seizure recurrence (Table 2).
We researched inpatient costs and length, which resulted
in a median of 1.5 days for the full study of seizures in patients who were admitted to the hospital. The costs are reported in Table 3.
Initial approach to first-time seizures in pediatrics
123
Table 1 Comparison of laboratory results.
Laboratory
Table 2 Treatment and recurrence of seizures.
Yes
No
Total
Normal
Abnormal
Not taken
12
0
1
12
2
4
24
2
5
BC and SE
Normal
Abnormal
Not taken
11
0
2
13
0
5
24
0
7
EEG
Normal
Abnormal
Not taken
4
9
0
13
5
0
17
14
0
Neuroimaging
Normal
Abnormal
Not taken
12
0
1
11
1
6
24
1
7
Lumbar
puncture
Normal
Abnormal
Not taken
1
0
12
4
0
14
5
0
26
HB
Treatment
Had seizure
Seizure recurrence
Yes
p
0.21
0.45
No
Total
Yes
9 (47%) 10 (52%)
19
No
4 (33%)
8 (66%)
12
13
18
31
Total
p
OR
0.69 0.55
95% CI
0.122.49
OR: Odd Ratio; CI: confidence interval.
Source: “Dr. José Eleuterio González” University Hospital of
the Universidad Autónoma de Nuevo León, 2012-2013.
0.02
Table 3 Costs.
0.14
0.06
Study
Cost
Number
Total cost
MRI
4,400
14
61,600
CT
2,759
10
27,500
1,150
31
EEG
HB: hematic biometry; BC: blood chemistry; SE: serum
electrolytes; EEG: electroencephalogram.
MXN Peso
48,050
MXN Peso
MRI: magnetic resonance; CT: computed tomography; EEG:
electroencephalogram; MXN: Mexican peso.
Discussion
The results of the study were not very distant from those
found in medical literature. With a similar reported incidence 4 of 4 seizure episodes for every 1,000 habitants,
which are said to be overstudied. This population was studied in full with at least one lab and/or clinical test, separating the EEG. Laboratory and neuroimaging tests were
performed in 77% of the patients. None of them were reported with significant results for the diagnosis and prognosis of the disease, only the EEG had a significant p lower
than 0.5, p=0.02.
Out of the 31 patients who had seizures, 45% showed an
abnormal EEG, and from these patients with electroencephalographic alterations, 64% suffered a recurrence,
compared to the rate reported in publications, which refers
to a recurrence rate of 71%.4
The results regarding the recurrence of seizures treated
with anti-seizure medication were similar to the data published. We prescribed treatment to 61% of the population.
Of the patients who received treatment, 47% had a recurrence (29% of the entire population); this data can be compared to medical literature which mentions a probability of
recurrence in a year of 19% to 26%. In this case the period of
time is a variable, whereas in our study we just monitored
the patients up to the first follow-up visit which is in a period of time no longer than 30 days.
This population showed a recurrence rate of 41% of the
patients in the follow-up visit, compared with 3 other studies which recorded the recurrence rate at 2 years: 37%,5
54% (95% CI=46%-62%)6 and 57%, respectively.7
Conclusion
First-time seizure study and diagnosis is based on the clinical study. EEG plays a major role in the study and classification of unprovoked seizures. The use of medications and
anti-seizure therapy after an unprovoked seizure is controversial; therefore each case should be personalized. The
doctor should adequately study recurrence risk factors in
order to start the patient on maintenance medication and
compare the benefits with the medication’s adverse effects.
Our population has similar incidence and recurrence rates
to those reported in the references, thus this study suggests
following the guidelines and recommendations made by the
American and European Pediatrics Association concerning
first-time unprovoked seizures.
Funding
References
1. Baumer J. Evidence based guideline for postseizuremanagement in children presenting acutely to secondary care. Arch Dis
Child 2004;89:278-280.
124
2. Adams S, Knowles P. Evaluation of a First Seizure. American
Academy of Family Physicians 2007;75-9:1344-1347.
3. Beghi E, Leone M, Solari A. Mortality in patients with a first unprovoked seizure. Epilepsia 2005;46:40-42.
4. Khan A, Baheerathan A. Electroencephalogram after first unprovoked seizure in children: Routine, unnecessary or case specific. Journal Pediatric Neurosci 2013;8:1-4.
5. Shinnar S, Berg AT, Moshe SL, et al. The risk of seizure recurrence after a first unprovoked afebrile sei-zure in childhood: an
extended follow-up. Pediatrics 1996;98:216-225.
J. A. Infante-Cantú et al
6. Stroink H, Brouwer OF, Arts WA, et al. The first unprovoked,
untreated seizure in childhood: a hospital based study of the
accuracy of the diagnosis, rate of recurrence, and long term
outcome after recurrence. Dutch study of epilepsy in childhood. J Neurol Neurosurg Psychiatry 1998;64:595-600.
7. Ramos Lizana J, Cassinello García E, Carrasco Marina LL, et al.
Seizure recurrence after a first unprovoked seizure in childhood: a prospective study. Epilepsia 2000;41:1005-1013.
medicina
universitaria
www.elsevier.com.mx
Original article
Prevalence of colonizing bacteria and their association with
primary bacteremias in hemodialysis of a university hospital
C. G. Quiñonez-Olivasa,*, I. M. Rivera-Moralesb, C. Sánchez-Martínezc, H. R. IbarraSifuentesa, R. O. Flores-Pérezc, J. A. Cárdenas-de la Garzad
Internal Medicine Department, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
a
Infectious Disease Service, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
b
Nephrology Service, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey,
N.L., Mexico
c
d
School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N.L., Mexico
Received: December 2013; Accepted: June 2014
KEYWORDS
Colonization; Primary
bacteremia;
Hemodialysis; Gramnegative bacilli;
Methicillin-resistant
Staphylococcus
aureus; Mexico.
Abstract
Introduction: The incidence of primary bacteremia in patients on hemodialysis (HD) is reported
to be from 2.5 to 5.5 cases per 1,000 catheter-day. The clinical impact is relevant and increases
the cost of the HD Unit.
Methods: The present study is the first of 2 phases. It was conducted from January to December
of 2012, and included all patients and nurses who were in the HD Unit. The prevalence of Gramnegative bacilli (GNB) and methicillin-resistant Staphylococcus aureus (MRSA) colonizing the nasal
passages and the skin is described. Also, phenotypic association was sought by genus, species and
sensitivities between colonizing bacterial strains and blood cultures with GNB and MRSA.
Results: The study included 70 patients and 10 nurses. The prevalence of nasal colonization in
patients by GNB was 9% and 6% in the pericatheter, and no nursing GNB colonization was discovered. The prevalence of MRSA nasal colonization was 19% and 6% in the pericatheter for patients and in the nurses the nasal colonization was 50% and 10% in the hands.
We identified 29 cases of primary bacteremia. The primary bacteremia rate is 1.5 per 1,000
catheter-day or 0.4 episodes per patient per year.
Conclusion: We demonstrated a high prevalence of MRSA colonization in patients and nurses in
the HD Unit. No relationship was found between primary bacteremia by GNB and patients and
nurses’ bacteria colonization by the phenotypic comparison.
* Corresponding author: Internal Medicine Department, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Gonzalitos Avenue, Mitras Centro, Monterrey, N.L., Mexico. Phone: (81) 8389 1111, ext. 3243, 3107. E-mail address: [email protected]
(C. G. Quiñonez-Olivas).
126
Introduction
The incidence of primary bacteremia in hemodialysis (HD)
patients is reported to be between 2.0% and 4.5% per 1,000
catheter-day, or one to 2 episodes per patient-year. The use
of HD catheters is a major mortality predictor in HD patients.1 Primary bacteremia is the most common cause of
morbidity and the second most common cause of mortality
in HD patients.2 Staphylococcus aureus (S. aureus) causes up
to 80% of vascular access infections and between 15% and
30% are caused by methicillin-resistant S. aureus (MRSA).3
Only a few studies have researched Gram-negative bacilli
(GNB’s) nasal and skin colonization.4 There are reports in
medical literature of a low incidence of catheter-related
GNB infections, theoretically it is attributed to those who
have a lesser adherence to vascular endothelial contrary to
Gram-positive cocci.5,6 GNB, which colonizes nasal mucus
and the pericatheter in patients in peritoneal dialysis has
not showed a major association with infections in the dialysis catheter’s exit point, nor in the development of peritonitis associated with peritoneal dialysis. 7,8 Conversely, a
discrete association between nasal and skin colonization by
GNB and vascular access infection in HD patients has been
demonstrated.8,9
The number of hemodialysis-related primary bacteremias
increased notoriously in our Hospital between 2010 and
2011, with a predominance of GNB in up to 60% of patients.
On the other hand, as described in medical literature, MRSA
is the causal pathogen of primary bacteremia with the highest morbidity; however its prevalence is unknown.
For this reason we focused this study on finding the prevalence of GNB and MRSA in patients and healthcare staff and
their association with primary bacteremia developed in the
HD Unit of the “Dr. José Eleuterio González” University Hospital.
Methods
The present study was conducted at the Renal Unit of the
“Dr. José Eleuterio González” University Hospital, from January to December of 2012, including all patients and nursing staff in the HD Unit. We used the following operational
definition for primary bacteremia: The presence of bacteria
in the blood stream in a patient with a vascular catheter for
over 48 hours, with positive hemoculture and clinical manifestation of infections without any other infectious focus.
The study was divided into 3 stages:
I. Supervision of a cohort of patients in the HD program in order to identify primary bacteremia cases and determine the rate of primary bacteremia
per 1,000 catheter-day and patient-year episodes.
We identified the patients who developed fever during HD and we performed a hemoculture to monitor them in the bacteriology lab and verify GNB
and MRSA isolations. We calculated the rate of primary bacteremia per 1,000 catheter-day and patient-year episodes.
II. Detection of patients colonized by GNB and MRSA
in nasal mucous and pericatheter skin, also detection of nasal mucous and hands colonization in the
C. G. Quiñonez-Olivas et al
nursing staff on the HD Unit; and determination
of the prevalence of colonization in both groups.
We performed a nasal swab culture and pericatheter skin in all patients in the HD Unit, and we performed nasal and predominant hand swabs in the
healthcare personnel involved in the connection of
patients in HD. Subsequently, we determined nasal
and skin colonization prevalence in both groups.
III.Determination of phenotypic association between
GNB’s isolated from primary bacteremias and GNBs
colonizing the nasal mucous and skin.
We identified bacteria genus and species in all bacteremia cases, as well as the colonizing strains,
using conventional biochemistry performed by the
clinical pathology lab. We carried out antibiotic
susceptibility testing (AST) in the following GNBs:
ceftazidime, ciprofloxacin and amikacin. In the S.
aureus we performed the AST to cefoxitin and if it
wasn’t sensitive to this antibiotic we determined
its methicillin resistance. We searched for an association between GNB’s isolated from primary bacteremia and colonizing GNB’s through phenotypic
comparison with genus, species and sensitivities
described in the antibiogram. In a second stage of
the same study we determined whether or not isolated MRSA’s were clones using pulsed field electrophoresis. The results were analyzed with descriptive
statistics in frequencies and proportions.
Results
We conducted colonization cultures from each of the 70 patients in the HD Unit. We documented nasal colonization in
47 patients (67%) and 50 isolations because 3 patients had 2
bacteria colonizing the nasal mucous. Pericatheter colonization was evidenced in 27 patients (39%) and 29 isolations
because 2 patients had 2 bacteria colonizing the pericatheter skin. The most relevant nasal and pericatheter skin-colonizing isolations can be found in Tables 1 and 2.
Table 1 Nasal colonizations in patients of the Hemodialysis
Unit of the “Dr. José Eleuterio González” University
Hospital.
Nasal
n=50*
Frequency
%
Methicillin-sensitive
Staphylococcus aureus
21
42
13
26
Escherichia coli
3
6
Klebsiella pneumoniae
1
2
Acinetobacter baumanii
1
2
Morganella morganii
1
2
*The frequencies do not add up to the total number of colonies
(n=50) because we did not add coagulase-negative
Staphylococcus, which is not considered a pathogenic flora.
Prevalence of colonizing bacteria and their association with primary bacteremias in hemodialysis of a
university hospital
Table 2 Bacterial colonies of pericatheter skin in patients
of the Hemodialysis Unit of the “Dr. José Eleuterio González”
University Hospital.
Pericatheter skin
n=29*
Frequency
127
Enterobacter
cloacae
%
14
48
4
14
Klebsiella pneumoniae
3
11
Pseudomona aeruginosa
1
3
Escherichia
coli
Pseudomona
aeuruginosa
(n=29) because we did not add coagulase-negative
Staphylococcus, which is not considered a pathogenic flora.
0
10
20
30
40
50
60
70
Figure 1 The percentage of each of the Gram-negative bacilli
isolated from the primary bacterimias.
Regarding healthcare personnel in the HD Unit, we documented nasal colonization in 10 nurses (100%) and 10 isolations. We found colonization in the predominant hand in 3
nurses (30%) and 3 isolations. The most relevant nasal and
predominant hand colonizations in healthcare personnel can
be found in Table 3.
The prevalence of nasal colonization in patients by MRSA
was 19% and by GNB, 9%; the prevalence in pericatheter
skin by GNB and MRSA was 6% for both. Regarding the nursing staff, the prevalence of nasal colonization by MRSA was
50% and 10% in the predominant hand; we did not find GNB
colonization.
During the study we identified 29 primary bacteremia cases confirmed microbiologically. The rate of bacteremia caused
by GNB was 28%, you can read each of the percentages
Table 3 Bacterial colonies in the nasal mucous and
dominant hand of the healthcare personnel of the
Hemodialysis Unit of the “Dr. José Eleuterio González”
University Hospital.
Nasal
n=10*
Frequency
%
5
50
4
40
Dominant hand
n=3*
Frequency
%
1
33
1
33
(n) because we did not add coagulase-negative Staphylococcus,
which is not considered a pathogenic flora.
on bacteremia-isolated GNBs in Figure 1. Primary bacteremias caused by S. aureus were 12 (67%) and 25% was by
MRSA, you can read each percentage of bacteremia-isolated
CGP in Figure 2. Primary bacteremia rate was 1.5 per 1,000
catheter-day or 0.4 episodes per patient-year. In the patients with isolations by GNB in their primary bacteremia
blood cultures, none of them displayed phenotypic association with nasal mucous and skin (Table 4).
Discussion
A low prevalence of GNB colonization in patients was demonstrated, with 6% and 9% for skin and nasal mucous respectively, similar to the rate described in medical literature.
Prevalence of MRSA colonization was 6% and 19% for skin and
nasal mucous respectively.10 In healthcare personnel, a prevalence of 10% in the predominant hand and 50% in nasal
mucous was demonstrated, between both groups this means
that at least one in every 3 individuals is an MRSA carrier.
Primary bacteremia rate was 1.5 per 1,000 catheter-day
or 0.4 episodes per patient-year, lower than the rate reported in international literature. 11 Bacteremias caused by
MRSA were 10%, but there is no previous information regarding
our grounds to compare to previous years. Primary bacteremias caused by GNB were 28%, representing a reduction of
over 50% of the cases identified as GNB in the years 2010 and
2011, during which it was 60% of the total of bacteremias. The
reduction of primary bacteremias by GNB during the present
study with regard to the last 2 years is probably caused by
hygiene actions performed by the nephrology department at
the beginning of that year, including the standardization of
asepsis of the pericatheter region with chlorhexidine, and having enough supplies for proper hand-washing, such as alcohol
antibacterials and electronic-sensor sinks.
In conclusion, an association between carriers (patients)
of GNB and primary bacteremias by GNB was not proved,
which is consistent with other epidemiologic studies. In
addition, a high prevalence of colonizing MRSA in patients
and nursing staff in the HD Unit was demonstrated.
128
C. G. Quiñonez-Olivas et al
Table 4 Example of the phenotypic association between Gram-negative bacilli. It shows that this Gram-negative bacilli with
the same genus and specie (i. e. Pseudomonas aeruginosa) colonizing (C) does not have the same antibiotic sensitivity as the
Pseudomonas aeruginosa isolated in bacteremias (B), which demonstrates that there is no association between the bacteria that
colonizes and that pathogenic bacteria isolated in the bacteremia hemocultures.
Bacteria
Amikacin
Ciprofloxacin
Ceftazidime
Pseudomona aeruginosa Bacterimia (B)
*09/07/12
Sensitive
Sensitive
Resistant
Pseudomona aeruginosa (B)
*15/07/12
Sensitive
Sensitive
Resistant
*16/07/12
Sensitive
Sensitive
Resistant
*04/08/12
Sensitive
Sensitive
Resistant
Pseudomona aeruginosa
Colonizing (C)
*23/04/12
Sensitive
Sensitive
Sensitive
*The dates show when the bacteria were isolated in the bacteremia and as a colony on the skin.
References
Enterococo
fecalis
Staphylococcus
coagulasa negativo
sensible a meticilina
resistente a meticilina
0
5 10 15 20 25
30 35 40 45 50
Figure 2 The percentage of each of the Gram-positive cocci
isolated from the primary bacterimias.
Funding
1. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the
prevention of intravascular catheter-related infections. Clinical infectious diseases: an official publication of the Infectious
Diseases Society of America 2011;52:162-193.
2. Alexander EL, Morgan DJ, Kesh S, et al. Prevalence, persistence, and microbiology of Staphylococcus aureus nasal carriage
among hemodialysis outpatients at a major New York Hospital.
Diagn Microbiol Infect Dis 2011;70:37-44.
3. Allon M, Daugirdas J, Depner TA, et al. Effect of change in
vascular access on patients mortality in hemodialysis patients.
American journal of kidney disease: the official journal of the
National Kidney Foundation 2006;47:469-477.
4. Katneni R, Hedayati, S Susan. Central venous catheter-related
bacteremia in chronic hemodialysis patients: epidemiology and
evidence-based management. Nature Clinical Practice Nephrology 2007;3:256-266.
5. Choi CS, Yin CS, Bakar AA, et al. Nasal carriage of Staphylococcus aureus among healthy adults. J Microbiol Immunol Infect
2006;39:458-464.
6. Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000;132:391–402.
7. Burton DC, Edwards JR, Horan TC, et al. Methicillin-resistant
Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997–2007. JAMA
2009;301:727–736.
8. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005;41:848–854.
9. Yazgi H, Ertek M, Ozbek A, et al. Nasal carriage of Staphylococcus aureus in hospital personnel and the normal population and
antibiotic resistance of the isolates. Mikrobiyol Bul
2003;37:137-142.
10. Kaplowitz LG, Comstock JA, Landwehr DM, et al. Prospective
study of microbial colonization of nose and skin and infection
of the vascular access in hemodialysis patients. J Clin Microbiol
1988;26:1257-1262.
11. Cisneros-Herreros J, Cobo-Reinoso J, Pujol-Rojo M, et al. Guía
para el diagnóstico y tratamiento del paciente con bacteremia.
Guías de la Sociedad Española de Enfermedades Infecciosas y
Microbiologia Clinica (SEIMC). Enfermedades Infecciosas y Microbiologia Clinica 2007;25:111-130.
medicina
universitaria
www.elsevier.com.mx
Scientific letters
Laryngeal amyloidosis: An uncommon cause of dysphonia
V. J. Villagómez-Ortiz*, M. Villegas-González, J. L. Treviño-González, R. SantosLartigue, B. González-Andrade, N. Montemayor-Peña
Otolaryngology and Head and Neck Surgery Departament, “Dr. José Eleuterio González” University Hospital, Universidad
Autónoma de Nuevo León, Monterrey, N.L., Mexico
Received: November 2013; Accepted: January 2014
KEYWORDS
Amyloidosis; Larynx;
Hoarseness; Congo
red; Vocal cords;
Mexico.
Abstract
Introduction: Amyloidosis is used to describe a range of disorders defined by extracellular deposition of abnormal protein fibrils. The larynx is the most common site of localized amyloidosis in
the head and neck region and constitutes less than 1% of benign laryngeal lesions. Hoarseness is
the most common symptom.
Objective: Prospective clinical evaluation of patients with localized laryngeal amyloidosis.
Clinical cases: Presented are 4 cases of patients with localized laryngeal amyloidosis who were
treated at the Otolaryngology and Head and Neck Surgery Department at the “Dr. José Eleuterio
González” University Hospital in Monterrey, Mexico. Three patients underwent phonomicrosurgery by direct microlaryngoscopy with the removal of the amyloid implantation using a cold
knife excision with great results. In each patient the major site of involvement was the supraglottis with a small focus on the false vocal cord. A medical work-up, including a complete blood
count (CBC), a basic metabolic panel, urinalysis, liver function test, chest X-ray and physical
examination were performed to rule out the presence of systemic disease; no amyloidosis or
signs of systemic disease were found. Congo red staining confirms the diagnosis of amyloidosis
in all surgical specimens.
Conclusions: In laryngeal amyloidosis, the treatment should be directed toward the improvement of the voice and the maintenance of the airway.
* Corresponding author: Otolaryngology and Head and Neck Surgery Departament, “Dr. José Eleuterio González” University Hospital.
Francisco I. Madero and Gonzalitos Avenue, Mitras Centro, Monterrey, N.L., Mexico. Telephone: (81) 8333 2917.
E-mail address: [email protected] (V. J. Villagómez-Ortiz).
130
Introduction
Amyloidosis is used to describe a range of disorders defined
by extracellular deposition of abnormal protein fibrils.
Amyloid deposits were first described by Von Rokitansky in
1842, and the term amyloid was first used by Virchow in
1851 to describe the reaction of this tissue to iodine and
sulfate.1 Borrow and Neuman (1873) were the first to report
laryngeal amyloidosis. Over 300 cases have been reported since then.2 Current classifications of amyloidosis are
based on the biochemical nature of the protein subunit
(Chastonay, Hurliman in 1986 and Lewis et al. in 1992). AL
amyloidosis (derived from light immunoglobulin chains) is
associated with systemic amyloidosis.
Fibrillar proteins have a characteristic pattern when observed under an electronic microscope after Congo red staining, displaying apple-green birefringence when examined
with polarized light.3
The larynx is the most common site of localized amyloidosis in the head and neck region and constitutes less than 1%
of benign laryngeal lesions.4 Hoarseness is the most common
symptom. The male-female ratio is 3:1, with an age range
between 8 and 80 years old, and a peak incidence occurring
in the 5th decade of life.5-7
There are different treatments and resection methods for
these lesions, though a few stand out, such as resection
with a CO2 laser and cold technique. Radiotherapy has recently been described in cases where the lesions cannot
be completely resected. Follow up is important in the
long term, because these lesions have a high recurrence
rate.3,4,8,9
Methods
Presented are 4 cases of patients with localized laryngeal
amyloidosis who were treated at the Otolaryngology and
Head and Neck Surgery Service at the “Dr. José Eleuterio
González” University Hospital in Monterrey, Mexico.
A flexible nasal fiber laryngoscopy was performed on all of
the patients. Lab studies were ordered to rule out the presence of a systemic disease: a complete blood count (CBC)
and basic metabolic panel, urinalysis, hepatic function test,
thoracic X-rays, and a full physical examination was performed, all of which were reported to be within normal parameters. Rectal or bone marrow biopsies were not performed.
Maximum phonation time, voice handicap index, reflux
symptoms (described by Belafsky et al.), and glottic
function and features in all patients were measured.
A resection by microlaryngoscopy with cold technique on
all the lesions was performed. Congo red stains were applied
to all surgical specimens.
The approval of the Ethics Committee of the “Dr. José
Eleuterio González” University Hospital was obtained, as
well as signed informed consents from all the patients.
V. J. Villagómez-Ortiz et al
Diagnosis and treatment were implemented to rule out
systemic involvement; the results were negative in all patients.
Resections of the lesions by microlaryngoscopy with cold
technique were executed, and samples were sent out for
histopathology analysis. Congo red staining was used, where
we were able to observe green birefringence through the
use of the electronic microscope.
The results of the questionnaires conducted before and
after the surgical procedure were documented. With the
use of this technique we were able to observe favorable results in the subjective symptoms as well as in the maximum
phonation time.
Case 1
A 67-year-old male, came to the Voice Clinic for the first
time presenting hoarseness with an evolution of 10 years,
progressive, vocal fatigue, glottic leak and inability to reach
high notes. He denies any systemic diseases or smoking. He
scored a glottic closure force index of 9, reflux index of 8
and quality of life index of 3.
At the physical examination: Maximum phonation time
was 17 seconds, S:Z ratio of 25:27. The videolaryngoscopy
displayed an elevated lump towards the right false vocal
cord and anterior commissure (Fig. 1).
Case 2
A 52-year-old female, teacher, came to the Voice Clinic as a
result of hoarseness with a 3-year evolution, accompanied
by vocal fatigue, vocal pauses and inability to reach high
notes. She did not improve by resting her voice. She denies
smoking or ethilism. She previously received steroids and
antibiotics without improvement.
Her glottic closure force index was 12, reflux index of 17
and quality of life index of 7. Her maximum phonation time
Cases presentation
A laryngeal amyloidosis diagnosis was performed on 3 men
and one woman, whose ages ranged from 14 to 67 years.
The most common symptoms are: hoarseness, pharyngodynia, vocal pauses, and vocal fatigue. The duration of the
symptoms before diagnosis was between 2 and 12 years.
Figure 1 Patient 1, first visit. An increase in submucus volume
can be observed in the photograph, altering the anatomy of the
false vocal cords at the supraglottic level.
Laryngeal amyloidosis: An uncommon cause of dysphonia
131
Figure 2 Patient 2, first visit. An increase in volume is observed in the left lower lip of the true vocal cord, creating premature contact upon glottal closure.
Figure 3 Patient 2, one month post-surgery. A lessening of the
increase in volume can be observed at the true vocal cords.
There is now no premature contact upon glottal closure.
was 7 seconds, S:Z ratio of 5:3. We were able to observe a
major glottis edema with the videolaryngoscopy (Fig. 2). A
phonomicrosurgery with cold technique was performed, and
the sample was sent for histopathological analysis with an
amyloidosis report.
Post-surgically, she showed an improvement in her maximum
phonation time to 12 seconds, a glottic force closure rate index
to 4, reflux index to 4, and a quality of life index of 3 (Fig. 3).
index of 18, maximum phonation time was 9 seconds, S:Z
ratio of 32:8. The videolaryngoscopy displayed an elevated
lump towards the right false vocal cord which impedes glottic closure, with a wide glottal gap (Fig. 4). A resection
using the cold technique was performed, and we confirmed
a diagnosis of amyloidosis. Post-surgical data: Glottic force
closure rate index of 10, reflux index of 5, quality of life index of 9, and maximum phonation time of 16 seconds (Fig. 5).
Case 3
Case 4
A 33-year-old male, presenting hoarseness with an evolution
of 3 years, accompanied by vocal fatigue, vocal pauses and
inability to reach high notes, occasional ethilism and denied
smoking.
At physical examination: Glottic leak, a glottic force closure rate index of 19, reflux index of 25, and a quality of life
A 14-year-old male with hoarseness, with a 2-year evolution, progressive, with vocal fatigue and vocal pauses during
conversation.
A videolaryngoscopy was performed, where we were able
to observe a lump which deformed both false and true vocal
cords, thus conditioning a premature glottic closure (Fig. 6).
Glottic force closure rate index of 13, reflux index of 10,
and a quality of life index of 6, maximum phonation time
was 12 seconds, S:Z ratio of 17:12 seconds.
Figure 4 Patient 3, first visit. Increased exophytic volume can
be seen, at the right level of the false vocal cords, which does
not obstruct the glottal light. And a plain deformity of the right
true vocal cord with premature contact and alteration of the
chordal wave vibration.
Figure 5 Patient 3, one month post-surgery. There is no evidence of supraglottic lesions, or obstruction of glottic light.
132
V. J. Villagómez-Ortiz et al
Figure 6 Patient 4, first visit. Submucous lesions at the left
false vocal cord level can be observed.
Figure 7 Patient 4, post-surgery. No evidence of lesions at the
supraglotic or glotic level.
The same surgical procedure was executed, and we sent a
sample for histopathological analysis. Post-surgical data:
Maximum phonation time of 21 seconds, glottic force closure rate index of 4, reflux index of 2, quality of life index of
5 (Fig. 7).
life. Diagnosis is confirmed by Congo red staining observing
an apple-green birefringence under an electronic microscope. Resection with cold technique is an adequate method to
remove lesions with positive subjective and objective results. It is important to rule out a systemic involvement in
these patients.
Discussion
The larynx is the most common site for primary amyloidosis
in the head and neck region. The male-female ratio in our
patients was the same as the one reported in medical literature, with a variation in age range.
In order of frequency, lesions were most commonly found
in the ventricle, vestibular folds, vocal folds, epiglottis, and
aryepiglottic folds. In our patients the most common was
the involvement of false vocal cords.
In general, the symptoms of this pathology are specific
and do not lead to diagnosis, thus requiring a high level of
suspicion, because they will appear depending on the size
and site of the lesion. The most common reported symptom
in our patients was hoarseness and vocal fatigue.
It is important to rule out the involvement of a systemic
disease in patients with this pathology. It is worth noting the
fact that in order to obtain our diagnosis, we did not perform any invasive procedures in our patients (i. e. rectal or
bone marrow biopsies).
The treatment for these patients is surgical, and a complete resection is essential to avoid recurrence; however,
there are few comparative studies between lesion resection
with cold technique and laser to estimate their recurrence.
Studies have suggested the use of radiotherapy combined
with surgery in those lesions where complete resection is
not possible.7
Conclusions
Laryngeal amyloidosis is a rare disease with a rate of 8 in
1,000,000 and a higher incidence during the 5th decade of
Funding
References
1. Green KM, Morris DP, Pitt M, et al. Amyloidosis of Waldeyer´s
ring and larynx. J Laryngol Otol 2000;114:296–298.
2. Gertz MA. Diagnosing primary amyloidosis. Mayo clinic proceedings 2002;77:1278–1281.
3. Biewend ML, Menke DM, Calamia KT. The spectrum of localized
amyloidosis: a case series of 20 patients and review of the literature. Amyloid 2006;13:135-142.
4. Gallivan, Gregory J. Laryngeal amyloidosis causing hoarseness
and airway obstruction. Journal of Voice 2010;24:235-239.
5. Aydin O, Ustundag E, Iseri M, et al. Laryngeal amyloidosis with
laryngocele. J Laryngol Otol 1999;113:361–363.
6. Nagasaka T, Lai R, Kuno K, et al. Localized amyloidosis and extramedullary plasmacytoma involving the larynx of a child.
Hum Pathol 2001;32:132–134.
7. Elphinstone J, McCafferty. Localized amyloidosis of the larynx.
Aust. J. Otolaryngology 1999;3:275–277.
8. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract.
Thorax 1999;54:444–451.
9. Neuner GA, Badros AA, Meyer TK, et al. Complete resolution of
laryngeal amyloidosis with radiation treatment. Head Neck
2012;34:748-752.
medicina
universitaria
www.elsevier.com.mx
Scientific letters
Surgical treatment of a pseudoaneurysm of the femoral artery
secondary to a gunshot wound. Clinical case report
M. A. Gómez-Álvareza,*, G. E. Muñoz-Maldonadoa, R. Salinas-Domíngueza, M. MercadoFloresb, J. A. Tamez-del Bosquea
General Surgery Services, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
a
b
Radiology Services, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey,
N.L., Mexico
Received: December 2013; Accepted: January 2014
KEYWORDS
Gunshot wound;
Femoral artery
aneurysm; Reversed
saphenous graft;
Mexico.
Abstract We report a case of a 18-year-old male patient with a diagnosis of pseudoaneurysm
of the right superficial femoral artery secondary to penetrating injury by gunshot, which was
treated in our Hospital with an aneurysm resection and a saphenous vascular graft inverted with
a satisfactory evolution.
Introduction
Trauma is the 3rd leading cause of death among the general
population. Vascular injuries represent 3% of everyday traumas with a high morbidity. Extremity pseudoaneurysms are
developed after penetrating trauma in 60% of arterial injuries. In 40% of those cases, the trauma is caused by a gunshot wound.1
In medical literature, we are able to find a series of small
amounts of cases; however, in a study by Yetkin et al., they
presented 8 patients with pseudoaneurysms located in the
femoral, popliteal and tibioperoneal arteries secondary to
gunshot wounds. They concluded that the diagnosis depends
on the high rate of suspicion by the healthcare provider, and
the longer the diagnosis takes, the more complications they
may have, up to loss of the limb.2
Case presentation
We report a case of a patient, male, 18-year-old with a gunshot wound in the right lower extremity that was assessed
in a different medical facility and was discharged without
* Corresponding author: General Surgery Services, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero and Gonzalitos
Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (81) 8346 7198. Cell Phone: 5566945497. E-mail address: [email protected] (M. A. Gómez-Álvarez).
134
an evident vascular injury. Four months after the incident,
the patient came to the General Surgery Department at our
Hospital for a consultation with pain in the right lower extremity and a limited gait. During physical examination a
pulsatile tumor of 9 x 7 x 9 cm in the external face of the
right thigh with the presence of a murmur in the femoral
region was documented; the rest of the extremity displayed
palpable pulse with a good intensity (Fig. 1).
We performed an angiotomography showing an arterial
aneurysm 10 x 8 x 7 cm originating from the superficial femoral artery with a continuity solution of 0.58 cm, which
communicated with the deep femoral artery (Figs. 2 and 3).
Our surgical strategy consisted of performing proximal
and distal vascular control of the superficial femoral artery,
complete resection of the superficial femoral artery aneurysm (Fig. 4) and placement of the inverted saphenous graft
(Fig. 5). The patient was discharged after a 7-day post-surgical stay, with a good evolution without complications, and
after a follow-up period of a year of consultations, the patient was reported as fully asymptomatic.
M. A. Gómez-Álvarez et al
Figure 1 Lump in anterior side outside of right thigh.
Discussion
Lower extremity pseudoaneurysms concur with global trauma statistics, being more frequent in young male adults.
The pathophysiology consists of the result of the energy dissemination of the surrounding tissue, the expansive wave,
projectile fragmentation or bone damaging the vascular
wall, injuring the endothelial and causing a thrombus.3
Chronic traumatic aneurysm is developed by the partial or
complete absorption of the periarterial hematoma at a fibrous sac level which is surrounded by the adjacent tissue.
In general, the term “traumatic aneurysm” is utilized to refer to pseudoaneurysms, whether they are acute or chronic.
Pseudoaneurysms must be treated as soon as possible, because of their risk of rupture or thrombosis.3 In our patient
the diagnosis was made 4 months after the event.
The typical clinical picture starts with a lump with progressive growth and pain and limitation in the extremity’s
functionality. During physical examinations there may be
tissue pallor and edema, and pulsations and bruits over the
lump. Most often there is an absence or decrease of intensity of the distal pulse; however, this is a critical point. In a
study by Peck, he concluded that it is possible to feel a distal pulse in 10% of patients with a severe arterial injury,4
just as with our patient.
The most common vascular injuries occur in the femoral
arteries (37.3%), as it was in our case, the popliteal arteries
(27.8%) and the axillary and brachial arteries (23.5%).1
The diagnosis is made through physical examination and
confirmed with an imaging study. The first study used is the
color Doppler ultrasound, because it is a non-invasive
method with excellent sensitivity and specificity which provides diagnostic, but not therapeutic, information. Even
though the “gold standard” is still the arteriography, more
importance has been given to non-invasive studies like the
angiotomography with 3D reconstruction. It is used because
of its diagnostic and therapeutic evaluation; it provides detailed information about the dimensions, morphology and
anatomy of the pseudoaneurysm.5 This was the study utilized in our case.
Figure 2 Computed axial tomography in coronal section
showing pseudoaneurysm of the superficial femoral artery.
When an aneurysm is larger than 2.5 cm, it is considered
“surgical” because of the risk of complications, such as a
thromboembolism or a rupture. The surgical treatment includes open surgical repair, compression and injection of
thrombin guided by ultrasound, embolization or endovascular repair with stent.3,5
Endovascular repair is not used routinely for the treatment
of femoral pseudoaneurysms. In general, it is used when the
patient presents contraindications for conventional surgery.6 Open surgical repair must be the first treatment option for late complications of arterial injuries such as fistulas
and pseudoaneurysms, using end-to-end anastomosis; however when it is not possible, an inverted saphenous venous
graft should be used, because it is more resistant to infection and has a longer duration,7 as was done in our case.
Therefore, we suggest our patients with penetrating
wounds located over the vascular trajectory to rule out a
vascular injury through an imaging study, even when there
is no clinical evidence of such injury. The risk of not diagnosing a vascular injury is the posterior emergence of an
Surgical treatment of a pseudoaneurysm of the femoral artery secondary to a gunshot wound. Clinical case report
135
Figure 5 Reversed saphenous graft in the femoral artery.
Figure 3 3D recontruction of the pseudoaneurysm of the femoral artery.
exclude possible complications when necessary. Despite all
the advances in endovascular interventionism, the first
treatment option for this pathology is conventional surgery
which consists of a resection of the pseudoaneurysm and
reconstruction with an inverted saphenous graft or a
prosthetic graft.
Funding
References
Figure 4 Pseudoaneurysm of the superficial femoral artery.
arterial-venous fistula or a pseudoaneurysm which can bring
severe complications if not treated in time, because they
can cause massive bleeding and possibly loss of the limb.
Conclusion
Currently, vascular injuries are rising with the increase in
violence and crime within society. Physical examination is not
enough in order to diagnose vascular injuries; therefore,
non-invasive and invasive methods must be used in order to
1. Uçar HI,Öç M,Doğan. Peripheral Vascular Injuries in Civilian
Population. Turkiye Klinikleri J Cardiovasc Sci 2006;18:132137.
2. Yetkin U, Bayrak S, Tetik B, et al. Surgical Approach to the
Pseudoaneurysms Of Lower Extremity Arteries Developed after
Gunshot Injuries. Journal of Thoracic & Cardiovascular Surgery
2007;10:2.
3. Rutherford RB. Diagnostic evaluation of extremity vascular injuries. Surg Clin North Am 1988;68:683-691.
4. Peck JJ, Eastman AB, Bergan JJ, et al. Popliteal vascular trauma. A community experience. Arc Surg 1990;125:1339-1343.
5. Feliciano DV, Mattox KL. Traumatic aneurysms. Vascular Surgery. 3rd edition. USA: Philadelphia, W.B. Saunders Company;
1989. p. 996-1003.
6. Ozisik K, Dural K, Okcu O, et al. Pseudoaneurysms of the popliteal and tibioperoneal arteries after gunshot injuries. J Trauma
2003;55:485-488.
7. Corriere MA,Guzman RJ. True and false aneurysms of the femoral artery. Semin Vasc Surg 2005;18:216-223.
medicina
universitaria
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Review article
Health effects due to exposure to polycyclic aromatic
hydrocarbons from the petroleum refining industry
M. T. Montaño-Soto, L. Garza-Ocañas*
Pharmacology and Toxicology Department, School of Medicine and “Dr. José Eleuterio González” University Hospital,
Universidad Autónoma de Nuevo León, Monterrey, N.L., Mexico
Received: January 2014; Accepted: May 2014
KEYWORDS
Polycyclic aromatic
hydrocarbons; Health;
Health impact
assessment;
Petroleum; Oil
refinery; Air
pollutants;
Environmental;
Mexico.
Abstract
Introduction: Polycyclic aromatic hydrocarbons (PAH) are a group of semi-volatile organic compounds composed of 2 or more aromatic rings, generated during incomplete combustion of organic matter. These compounds have been considered as major air pollutants, and also, there is
evidence of potential mutagenic and carcinogenic effects in some of them. One of the most
important sources of these compounds is industry, and particularly, in processes such as aluminium or coke production, waste incineration and petrochemical and oil refining. This last process is the subject of this article, whose aim is to review the health effects in persons potentially exposed to PAH generated during petroleum refining.
Methods: A descriptive review of the available literature was performed, in which PubMed was
used as an information source. The following search descriptors were used: refinery, PAH,
health, health impact assessment, air pollutants and environmental, as well as their translations in Spanish.
Results: Eleven articles were included, and most of them correspond to epidemiological studies
in which a high incidence of cancer is reported.
Conclusions: The reviewed studies concur that there is a significant relationship between the
presence of oil refineries and the increase of adverse health effects of workers and people living
in areas that are close to these industries, particularly, respiratory diseases and cancer. However, it is important to develop studies that simultaneously evaluate the effects on human health
and the concentration of these substances in the environment, in order to establish a more direct relationship between the 2 variables.
* Corresponding author: Pharmacology and Toxicology Department, School of Medicine and “Dr. José Eleuterio González” University Hospital. 235 Gonzalitos Street, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico. Telephone: (+52 81) 8329 4201.
E-mail address: [email protected] (L. Garza-Ocañas).
Health effects due to exposure to polycyclic aromatic hydrocarbons from the petroleum refining industry
137
Introduction
The refining industry as a PAH source
Evidence shows an increasing correlation between environmental pollution and health effects on an exposed population.1 By the year 2006 the World Health Organization (WHO)
estimated that between 23% and 24% of the world’s morbidity/mortality was attributable to environmental factors,
and of the considered conditions the ones associated with
air pollution occupied 2nd place.2
Among major air pollutants representing health risks are
polycyclic aromatic hydrocarbons (PAH), which can be found
in the gas phase or well-bonded to particulate matter (PM).3
PAHs are a group of semi-volatile organic compounds composed of 2 or more aromatic rings, generated during incomplete combustion of organic matter. During this process
molecule and radical fragments are combined, thus creating
these substances.3 These compounds are major environmental pollutants because they are considered to be potentially
carcinogenic and mutagenic, hence considered “air quality
markers” in terms of the health risks their presence represents.4-10
According to the United States (US) Environmental Protection Agency (EPA), out of the 100 substances of this kind
listed, 16 are catalogued as “priority pollutants” (Table 1)
based on the following criteria: toxicity, human exposure
potential and frequency of occurrence in hazardous waste
sites.9-11
Undoubtedly oil refining’s final products are currently one of
the most important energy sources for the industry as well
as for most people’s everyday life. However, over the past
few years, this activity has been strongly connected to the
presence of high PAH concentrations in locations close to
these types of facilities.12-20 At most of these sites PAH levels
have been quantified even above those reported at areas
with major vehicular traffic.
Consequently, different authors have researched the
health effects as a result of the exposure to this type of industry, in people exposed occupationally and environmentally. Thus the objective of this study is to conduct a descriptive
review of the available literature in which they show the
main health effects linked to PAH exposure from the oil refinery industry.
PAH presence in the environment
PAHs are generally found in the environment as complex
combinations, practically in every substrate, their accumulation is the result of emission rates exceeding the capability of natural degradation.12 They can be released into the
environment through natural sources such as forest fires and
volcanic eruptions; however in recent years anthropogenic
emissions have been responsible for the increase of these
substances in the environment. Among the main sources of
anthropogenic origin are: domestic, mobile, agricultural and industrial emissions.9
Despite the fact that the industry in general is considered
an important source of PAH emission into the environment,
the activities that emit the largest PAH amounts are: primary aluminum production, coke production, waste incineration, fossil-fuel-based power generation, the petrochemical
industry, and crude oil refineries.9,10
Methods
Available literature was identified performing a web search.
We used PubMed’s database as a source of information, as
well as Science Direct, EBSCOhost and Springer, through the
General Direction of Libraries of the Universidad Autónoma
de Nuevo León (UANL, by its Spanish acronym). We used the
following terms and combinations as search criteria (and
their Spanish equivalents): oil refinery AND polycyclic aromatic hydrocarbons [MeSH] AND health [MeSH], oil refinery
AND health [MeSH], OR health impact assessment [MeSH],
oil refinery AND air pollutants [MeSH], OR environmental impact [MeSH], these last 2 combinations were used to examine the environmental PAH presence in areas located close to
oil refineries. The search was not limited to newer articles,
thus we used all available literature to date.
Results
We obtained a total of 87 articles, from which we selected
11. The excluded articles were those that did not evaluate
sanitary effects of exposure during oil production or those
where they evaluated the effects in other organisms (like in
Salmonella in the “Ames Test”), or by other pollutant sources.
The articles where work exposure was evaluated correspond to 3 epidemiological studies developed for the purpose
of correlating the increase in cancer incidence and work activity in refineries. They used work records, national survey
demographic data, national cancer and epidemiological
Table 1 Substances prioritized for their carcinogenic and mutagenic potential.
Naphthalene
Acenaphthene
Acenaphthylene
Fluorene
Phenanthrene
Anthracene
Fluoranthene
Pyrene
Benzo (a) anthracene*
Chrysene
Benzo (b) fluoranthene*
Benzo (k) fluoranthene*
* Carcinogens.
Source: US Environmental Protection Agency (EPA).10
Benzo (a) pyrene*
Dibenzo (ah) anthracene*
Benzo (ghi) perylene
Indeno (123-cd) pyrene*
138
surveillance records from different countries. Of the studies
that evaluated environmental exposure, 4 of them linked
exposure and cancer incidence, 2 of them linked the distance to the refineries and cancer incidence, and one linked
exposure with effects over gestation time and another one
with pulmonary function in children. Table 2 is a list of the
main findings in this review.
In 1991, in a study conducted in Australia by Christie et
al., where they evaluated cancer incidence in the Australian
oil industry from 1981 to 1989, observed an increase of approximately twice as many cases of cancer than expected in
employees of the different oil companies operating in the
country, including refineries, production facilities, warehouses and distribution centers. The most common cancer types were lung cancer and pleural cancer, which have been
linked to PAH exposure, as well as non-Hodgkin lymphoma,
multiple myeloma and leukemia, the latter of which has
been mainly linked to benzene exposure. Benzene is also an
aromatic obtained during oil refinery, however, this has the
characteristic of being volatile, and this substance as well
as PAHs have been strongly connected to cancer development.21
Similar results were presented by Järvholm et al., in Sweden, where a cohort study was conducted, including 4,319
Swedish workers (4,128 men and 191 women) who worked
for at least one year in the oil industry. Cancer incidence
within these workers was compared to cancer incidence within the general population, and in the results it was
reported that refinery operators presented a statistically
significant increment in the development of leukemia (6 cases vs. 1.7 expected, 90% confidence interval [CI] of relative
risk) in comparison to the general population.22
On the other hand, in the year 2000, Wong and Raabe
conducted a meta-analysis based on a review of 28 cohort
studies, which included over 350,000 oil workers in countries like US, United Kingdom (UK), Canada, Australia, Italy,
Sweden and Finland, during an observation period of 60
years (1937-1996). In their results a significant increase in
the risks of melanoma in 2 studies in the UK stand out, and
prostate cancer in a couple of studies in the US.23
For different authors it is reasonable to consider that if
occupational exposure to the oil industry pollutants increases incidence of diseases in workers, then environmental
and non-occupational exposure to these pollutants can also
cause an increase in the incidence of certain diseases among
residents of areas located close to this type of industry.24-28
Under the same hypothesis several papers have been developed where they evaluate the effects in the open population who live in areas close to refineries. The results of some
of these studies suggest an important connection between
cancer incidence and the proximity to refineries.
Since the early 1980’s in the US a study was conducted
where they determined cancer incidence in places located close to a refinery along the coast of California. This
study showed a growing and statistically significant trend
(p<0.05) of cancer in the oral cavity and pharynx, stomach,
trachea, bronchi, lung, prostate, kidney and urinary organs,
in men, while in women they observed a statistically significant increase in oral cavity and pharynx cancer.24
In Taiwan, they evaluated if lung cancer mortality in women was linked with residence adjacent to an oil refinery. In
this country lung cancer is the second cause of cancer
mortality in men and the main cause for women. Results
showed that women with a higher exposure to the petrochemical industry presented a higher risk of developing lung
cancer in comparison to the group who lived in locations
with low petrochemical atmospheric pollution.25
On the other hand, Barregard et al. conducted a study in
Sweden, where they evaluated leukemia incidence in an
area down-wind from a big oil refinery. In their results they
observed an increase in leukemia incidence in the population living in sites affected by the winds from the refinery,
Table 2 Evaluated health effects.
Health effects
Author
Year
1
2
Christie
(1991)
X
X
Järvholm
(1997)
Wong
(2000)
Kaldor
(1984)
X
X
Yang
(1999)
Barregard
(2009)
Axelsson
(2010)
Wilkinson
(1999)
Zusman
(2012)
Yang
(2004)
Wichmann
(2004)
3
4
5
6
7
8
9
10
11
X
X
12
13
14
X
X
X
X
X
X
X
X
X
X
X
X
-
-
-
X
X
X
X
X
1: lung cancer; 2: pleural cancer; 3: skin cancer; 4: bladder cancer; 5: prostate cancer; 6: oropharyngeal cancer; 7: stomach cancer; 8:
trachea cancer; 9: kidney cancer; 10: non-Hodgkin lymphoma; 11: multiple myeloma; 12: leukemia; 13: preterm birth; 14: pulmonary
function.
Health effects due to exposure to polycyclic aromatic hydrocarbons from the petroleum refining industry
and that in a 10-year period (1995-2004), the number of
cases doubled the expected numbers for this particular disease.26 Just as the reports by Christie (1991) and Järvholm
(1997), they considered that leukemia development is
linked to benzene exposure, more than to PAH exposure.
Contrary to the results reported by Barregard (2009), Axelsson et al. (2010) conducted a study in the Stenungsund region
in the same country. Said study included cancer records from
1974 to 2005, specifically leukemia, lymphoma, liver cancer,
and brain cancer. In their results they did not present significant differences between the total of observed cases and the
number of expected cases, for any cancer type, consequently
the author concludes that for this area cancer incidence was
not affected by industrial emissions from refineries.27
Moreover, as a response to the public and scientific preoccupation of the possible risks involved in living near refineries, Wilkinson et al. (1999) conducted a study which
included 11 refineries in Great Britain, where they evaluated the incidence of lympho-hematopoietic diseases linked
to refinery pollutant exposure. The analysis was performed taking into account the distance between refineries and
the place where the individuals included in the study lived,
for this purpose they established 8 rings around the refineries’ perimeters with a maximum distance of 7.5 Km. In their
results, they observed a decline in the risk of Hodgkin lymphoma as the distance from the refineries increased.28
Zusman et al. also associated the risks of cancer linked to
living in the proximity of an industrial area with the presence of oil refineries and oil and petrochemical storage facilities. Their results are very similar to Wilkinson’s, because
they showed that lung cancer and non-Hodgkin lymphoma
incidence tended to decrease as the distance to storage facilities increased, especially among the elderly.29
Another important health effect on the population living
near refineries is the rise in the incidence of premature births. Regarding this issue, in Taiwan they evaluated its incidence in infants born within 3 towns located 3 Km from oil
refineries. The amount of considered births was 7,095 (cases)
and 57,483 (controls), results showed an adjusted odds ratio
of 1.14 (95% CI) for premature births when they compared
refinery areas and control zones, these results provide evidence of the link between living in areas with atmospheric
pollution caused by oil refineries and premature birth risk.30
Furthermore, in Argentina they evaluated the impact on
respiratory health in children, under the hypothesis that
children who live near refineries and petrochemical plants
would have more serious health consequences, compared to
those children who live in areas outside this source. In this
study, they considered 181 children from 4 different areas
(industrial, urban and 2 control sites). In order to evaluate
their pulmonary function a spirometry was performed on
every child as well as a survey. Results showed that children
who lived in the industrial region showed a significant increment in adverse side effects in respiratory health, presenting a higher asthma prevalence (p<0.001), more asthma
exacerbations (p<0.001), and more respiratory symptoms
(p<0.001), as well as diminished respiratory function.31
Conclusions
Without a doubt, air pollution because of industrial emissions has become a matter of concern more and more due to
139
its harmful effect on the health of the population. Different
researches show that the industry’s growth in urban areas is
frequently connected to high levels of atmospheric pollutants, at the same time these levels are connected to the
rise and exacerbation of different diseases.32
Nevertheless, there is no evidence of the health impact of
all environmental pollutants. While PAHs are considered to
be potentially carcinogenic and mutagenic, and thus we
could consider them responsible for the health impact caused by exposure to refinery emissions, according to the reviewed literature we can conclude that PAHs are not the only
ones participating in this process. In some cases, the effect is
on bone marrow cells. Leukemia, non-Hodgkin lymphoma
and multiple myeloma, are more connected to exposure to
compounds such as benzene, while lung, airways, urinary
tract and skin cancer, have been related more to PAH exposure.
Thus, we are not overlooking the fact that atmospheric
pollution corresponds to a complex mixture of different toxic substances and from different sources that can hardly be
identified.
Therefore, we suggest the development of environmental
evaluations that allow us to identify organic compounds like
PAH in different substrates, developed simultaneously with
studies of the health impact in exposed populations in order
to establish more direct connections with the health effects
in humans and the emission source of these compounds.
Funding
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14. Rao B, Ansari M, Pipalatkar P, et al. Monitoring and assessment
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2007;79:197-201
15. Tiwari J, Chaturvedi P, Ansari N, et al. Assessment of Polycyclic
Aromatic Hydrocarbons (PAH) and Heavy Metals in the Vicinity
of an Oil Refinery in India. Soil and Sediment Contamination
2011;20:315-328.
16. Yassaa N, Cecinato A. Composition of torched crude oil organic
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17. Cazier F, Dewaele D, Delbende A, et al. Sampling analysis and
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18. Rehwagen M, Müller A, Massolo L, et al. Polycyclic aromatic hydrocarbons associated with particles in ambient air from urban
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19. Di Filippo P, Riccardi C, Pomata D, et al. Seasonal Abundance of
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medicina
universitaria
www.elsevier.com.mx
Voices of doctors and patients
The new generation of residents
E. M. Treviño-Salinas*
Obstetrics and Gynecology Department, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo
León, Monterrey, N.L., Mexico
Received: May 2014; Accepted: June 2014
The new generation of medical professionals keeps growing
and evolving, along with technology in the medical field, as
well as our responsibility to form generations of qualified
graduates to address the current population’s demands.
This generation goes hand in hand with virtual medicine;
although a useful tool, it involves the development of fewer
interpersonal skills. Perhaps in other fields outside the natural sciences, social interactions through virtual means and
virtual work activity can form successful professionals, yet
not in the medical field, where the doctor-patient personal
relationship is still essential in order to form integral medical professionals.
Discipline and respect of hierarchies, in my opinion, has
decreased from generation to generation, which leads to a
loss of values such as punctuality, pulchritude, and perfectionism; thus, a deficiency in clinical skills, resulting in medical professionals unable to make a proper clinical history,
a reliable physical examination, interpret information, and
establish a diagnosis with logic and communication.
The so-called Burnout syndrome, which exist, and always
have, is a part of our residents’ formation, who must work
long shifts and learn how to manage stress and fatigue. This
is not only part of their formation as a specialist but a taste
of the work performed once they have graduated, keeping
in mind at all times that we are working with human beings
and that we are responsible for their health regardless of
time, stress or personal issues, as we pronounce in the Hippocratic Oath.
Even though the internet is a tool of great value for medical attention, it by no means replaces the importance of
personalized gadget-free care. Technology should be used
and it is of great help in becoming experts in requesting all
kinds of tests and procedures, yet technology does not
always help us understand when to request them or how to
interpret them. Thus we could fall into a laboratory-oriented, instead of a patient-directed, perspective.
Although values have changed, tenacious effort, pride,
devotion to work, strict responsibility and the pursuit of excellence should still be the norm. University hospitals are
highly prestigious institutions whose function, in addition to
offering medical care of excellence, is to train high-level
medical personnel. This involves a great responsibility and
the requirements and demands required from post-graduate
medical professionals should be higher than in other hospitals.
We, the teachers, need to recognize that our duty is to
educate, supervise and explain pathophysiology, clinical
symptoms and the natural history of diseases. We must be
present in the learning of the residents and teach them to
know which tests to order, when to do it and how to interpret them, teach them to use technology and the internet
to verify rather than formulate their clinical impressions.
We need them to learn the value of a good clinical history and a proper physical examination; to know how to think
and be responsible, teach them that the value of hierarchy
doesn’t only reside in the number of years of residence, but
* Corresponding author: Obstetrics and Gynecology Department, “Dr. José Eleuterio González” University Hospital. Francisco I. Madero
and Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N.L., Mexico (E. M. Treviño-Salinas).
142
that every resident has surgical, caregiving and service
work, teaching work to residents lower in the hierarchy and
shouldering the great responsibility of demanding, reviewing and supervising each and every one of their actions
performed with every one of their patients. Residents must
acquire sufficient experience with responsibility, which any
medical professional who graduated from our university
should have.
E. M. Treviño-Salinas
The resident should be responsible enough to study his/
her patients and their pathologies and be able to continue
offering quality care. Being a medical professional is a vocation of service to others, without major personal considerations. And we, as teachers at a University Hospital, must
be responsible leaders, committed and with a high social
standards.
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Expert’s corner: a personal approach
How we study and treat patients with suspected thrombophilia
G. J. Ruiz-Argüelles*, G. J. Ruiz-Delgado
Center for Hematology and Internal Medicine, Clínica Ruiz de Puebla, Puebla, Pue., Mexico
Received: April 2014; Accepted: June 2014
Since 1999 we have been studying and treating patients
with suspected inherited and/or acquired thrombophilia.
Some of them have been referred to us by other specialists,
mainly ophthalmologists and neurologists, but interestingly,
most of them have come to our clinic referred to by friends
or relatives, this being most likely, to our regret, a reflection of the importance that other specialists place on this
condition.
Diagnosis
Inherited thrombophilia is a rather common condition which
explains several cases of thrombosis. An inherited thrombophilic condition should be suspected in cases of: Thrombosis
in individuals of less than 45 years, thrombosis in unusual
sites, thrombosis without other triggering conditions, resistance to antithrombotic treatments, recurrent miscarriages
and a family history of thrombosis. Most cases of thrombosis
in these persons present themselves when exposed to other
acquired thrombophilic conditions, the most frequent ones
being estrogen treatment, puerperium and prolonged immobilization.
In the vast majority of cases, patients coming to our clinic
have been studied incompletely by other physicians and given empirically antiplatelet drugs, anticoagulants or both.
Many of these patients have been frightened by their physicians about having a potentially mortal disease at a young
age.
a) Thrombophilic screening
Stemming from our studies of more than 15 years, we have
designed 2 thrombophilic screening sets of studies in Mexican patients being studied for thrombophilia. Table 1 shows
the salient inherited thrombophilic conditions which we
have identified in Mexicans and which were used to design
these 2 thrombophilic profiles:
1. Full thrombophilic screening profile: MTHFR C677T
gene mutation, investigation of the sticky platelet
syndrome, activated protein C resistance aPCR
phenotype, factor V Leiden mutation, HR2 haplotype of the factor V gene, anti-phospholipid antibodies, factor II G20210A gene mutation, protein C
levels, protein S levels, antithrombin III levels, PNH
phenotype in red and white blood cells, JAK-2
V617F gene mutation, and lupus anticoagulant
2. Limited thrombophilic screening profile: MTHFR
C677T gene mutation, investigation of the sticky
platelet syndrome, aPCR phenotype, and antiphospholipid antibodies.
We encourage all patients to have the full laboratory
workup done, since the chances of identifying the thrombophilic conditions are above 90%, provided all the workup is
done. We reserve the limited profile for patients who are
unable to defray the cost of the full workup. Before making the set of studies, we instruct the patients to stop both
* Corresponding author: Center for Hematology and Internal Medicine. 3710 8B Sur Street, Z.P. 72530, Puebla, Pue., Mexico. Telephone:
01 (222) 243 8100. Fax: 01 (222) 243 8428. E-mail address: [email protected] (G. J. Ruiz-Argüelles).
144
G. J. Ruiz-Argüelles, G. J. Ruiz-Delgado
Table 1 Prevalence of several thrombophilic conditions in
both thrombophilic Mexicans mestizos and normal controls.
significance. On the other hand, the prevalence of this mutation in the normal population in Mexico is extremely high.
Since this mutation may lead into hyperhomocystinemia
which may be aggravated by folic acid deficiency, we recommend folic acid, 5 mg/day, indefinitely to individuals
displaying this gene mutation and having suffered a thrombotic episode.
Thrombophilics
Normal
controls
MTHFR C677T gene mutation
67
78
Sticky platelet syndrome
57
15
Factor V gene HR2 haplotype
21
8
c) Activated PCR aPCR phenotype
Activated protein C resistance phenotype
20
2
Anti-phospholipid antibodies
15
3
Factor V gene Leiden
mutation
13
0.7
Factor II gene G202010A
mutation
11
0
Coagulation protein C
deficiency
7
0
Coagulation protein S
deficiency
6
0
This condition can be either inherited or acquired. In Mexicans mestizos the acquired forms (antiphospholipid antibodies, increased factor VIII levels) are considerably more
frequent. Patients with inherited forms of aPCR who have
had a thrombosis probably need an anticoagulant indefinitely. We tend to use the new oral anticoagulants (NOACs)
more than vitamin K antagonists and prefer rivaroxaban
which is used once a day. Individuals with acquired forms of
aPCR need the anticoagulant at least while the laboratory
phenomenon is present.
Anti-thrombin III deficiency
1
0
Factor V gene Hong Kong
mutation
1
0
antiplatelet drugs and/or anticoagulants, and to switch into
low molecular weight heparin 5-7 days before drawing the
blood samples. Most of the times we identify 2 or more inherited thrombophilic conditions which coexist with another
acquired thrombophilic state in order to develop a full
blown thrombotic episode.
Treatment
Once the diagnosis is done, employing the above mentioned studies, we make the following recommendations to the patients:
a) Sticky platelet syndrome (SPS)
This inherited condition leads into both arterial and venous
thrombosis and, until recently, its true importance in medical literature had been neglected. Patients with the SPS
rethrombose when given oral anticoagulants; they must be
treated with antiplatelet drugs. Aspirin (100 mg/day) is adequately tolerated by more than 90% of patients; the rest are
to be given clopidogrel or other antiplatelet drugs. The test
to define SPS must be repeated 4 weeks after starting aspirin; if the aggregation profiles normalize it must be kept
indefinitely; less than 10% of individuals need other antiplatelet drugs to reverse the platelet hyperaggregability. SPS
patients, adequately treated, have a less than 5% chance of
re-thrombosing.
b) MTHFR C677T gene mutation
This genetic condition probably is not, by itself, enough to
create thrombophilia, but added to other ones, it may have
d) Other inherited conditions
Protein S deficiency, protein C deficiency and anti-thrombin
III deficiency, all of them very infrequent in Mexicans mestizos, probably need lifelong anticoagulation. Again, we tend
to use the NOACs more than vitamin K antagonists and prefer rivaroxaban which is used once a day. NOACs are significantly more expensive than vitamin K antagonists, but in
the long turn, needing no laboratory control and being less
related to severe hemorrhages, may be a good option.
Conclusion
With a full laboratory workup, we are now able to identify
inherited and acquired thrombophilic conditions in more
than 90% of individuals having a clinical marker of thrombophilia. These studies should ideally be done in persons studied
and treated by cardiologists, angiologists, gastroenterologists,
neurologists, gynecologists, ophthalmologists and other specialists dealing with either arterial or venous thrombosis, in
order to properly identify the conditions and prevent future
re-thrombotic episodes. Even hematologists still consider these studies and treatments as experimental or non-evidencebased. As a result of studying these conditions in more than
500 Mexicans mestizos, we have been able to define thrombophilic profiles, which could be used to both identify these
diseases and define the more adequate treatment.1-16
References
1. Ruiz-Argüelles GJ, González-Estrada S, Garcés-Eisele J, et al.
Primary thrombophilia in México: A prospective study. Am J Hematol 1999;60:1-5.
2. Ruiz-Argüelles GJ, Garcés-Eisele J, Reyes-Núñez V, et al. Primary thrombophilia in México II: Factor V G1691A (Leiden),
prothrombin G20210A and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos. Am
J Hematol 2001;66:28-31.
3. Ruiz-Argüelles GJ, López-Martínez B, Cruz-Cruz D, et al. Primary
thrombophilia in México III. A prospective study of the sticky platelet syndrome. Clin Appl Thromb Hemost 2002;8:273-277.
How we study and treat patients with suspected thrombophilia
4. Ruiz-Argüelles GJ, Ruiz-Delgado GJ, López-Martínez B. El «síndrome de las plaquetas pegajosas”: Una causa frecuente pero
ignorada de trombofilia. Rev Invest Clín Méx 2002;54:394-396.
5. Ruiz-Argüelles GJ, Poblete-Naredo I, Reyes-Núñez V, et al. Primary thrombophilia in México IV: Leiden, Cambridge, Hong
Kong, Liverpool and HR2 haplotype polymorphisms in the factor
V gene of a group of thrombophilic Mexican Mestizos. Rev Invest Clín Méx 2004;56:600-604.
6. Ruiz-Argüelles GJ, López-Martínez B, Valdés-Tapia P, et al. Primary thrombophilia in México V: A comprehensive prospective
study indicates that most cases are multifactorial. Am J Hematol 2005;78:21-26.
7. Ruiz-Argüelles GJ, González-Carrillo ML, Reyes-Núñez V, et al.
Trombofilia primaria en México, parte VI: Falta de asociación
estadística entre las condiciones trombofílicas heredadas. Gac
Méd Méx 2007;143:317-322.
8. Garcés-Eisele J, González-Carrillo ML, Reyes-Núñez V, et al.
Primary thrombophilia in México VII: the V617F mutation of
JAK2 is not a frequent cause of thrombosis. Hematology
2008;13:244-246.
9. Ruiz-Argüelles GJ, Alarcón-Urdaneta C, Calderón-García J, et
al. Primary thrombophilia in México VIII: Description of five kindreds of familial sticky platelet syndrome phenotype. Rev Hematol Méx 2011;12:73-78.
145
10. Ruiz-Argüelles GJ, Garcés-Eisele J, Camacho-Alarcón C, et al.
Primary thrombophilia in Mexico IX: The glycoprotein IIIa PLA1/
A2 polymorphism is not associated with the sticky platelet syndrome phenotype. Clin Appl Thromb Hemost 2013;19:689-692.
11. Moncada B, Ruíz-Argüelles GJ, Castillo-Martínez C. The sticky
platelet syndrome. Hematology 2013;18:230-232.
12. Velázquez-Sánchez-de-Cima S, Zamora-Ortiz G, Hernández-Reyes J, et al. Primary thrombophilia in México X: A prospective
study of the treatment of the sticky platelet syndrome. Clin
Appl Thromb Hemost 2013;Sep 19. [Epub ahead of print]
13. Césarman-Maus G, Villa R, Kubisz P, González-Ramírez M, et al.
El síndrome de plaquetas pegajosas. Rev Hematol Méx
2013;14:149-153.
14. Ruiz-Argüelles GJ. Comment on sticky platelet syndrome. Semin Thromb Hemost 2014;40:273.
15. Ruiz-Argüelles GJ, Ruiz-Delgado GJ. Trombofilia. En: Ruiz-Argüelles GJ, Ruiz-Delgado GJ (editores). Fundamentos de Hematología. 5ª Edición. México: Editorial Médica Panamericana;
2014. p. 327-336.
16. Kubisz P, Ruiz-Argüelles GJ, Stasko J, et al. Sticky platelet syndrome: History and future perspectives. Semin Thromb Hemost
2014 Jun 9. [Epub ahead of print].
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Expert’s corner: a personal approach
Managing functional dyspepsia
Á. R. Flores-Rendón*
Gastroenterology and Digestive Endoscopy Service, Social Security and Services for Government and Municipal Workers of
Baja California ISSSTECALI, Mexicali Hospital, Mexicali, B.C., Mexico
Received: May 2014; Accepted: May 2014
Functional dyspepsia is a highly prevalent disease worldwide. Its symptoms are manifested as pain (burning or not) in
the upper abdomen and early satiety, postprandial fullness,
bloating, nausea and belching. For its study and treatment,
it is divided into 2 syndromes: epigastric pain, which is meal
unrelated, and postprandial distress, which as the name suggests, are meal related symptoms. These 2 syndromes frequently overlap.1
The term functional dyspepsia implies a patient with upper
digestive symptoms whose endoscopy reveals a normal stomach and duodenum or with minimum changes, the Rome III
criteria diagnoses this disease; nevertheless, recent studies
suggest the need to modify the temporality criteria.
Categorizing patients into 2 syndromes has therapeutic
implications, which are based on pathophysiological mechanisms, considering that patients with epigastric pain may
have hypersensitivity or a Helicobacter pylori (H. pylori) infection, while patients with postprandial distress may suffer
fundic-relaxation or gastric emptying issues.
Within the therapeutic approach of functional dyspepsia,
there are important pharmacological and non-pharmacological measures, including:
Non-pharmacological measures
a.Diet
We suggest avoiding foods such as: soft drinks, coffee, tea,
chocolate, mint, peppermint, garlic, onion, tomato, pepper,
gum, spices and citrus, as well as excessive amounts of fruit
and vegetables, especially when symptoms suggest problems with gastric emptying. Once the patient improves,
these foods should be re-introduced in an orderly fashion to
test tolerance.
b.Upper gastrointestinal (GI) endoscopy
It is necessary for a functional dyspepsia diagnosis, yet not
for all patients. Indications include: recent onset dyspepsia
in people older than 50, weight loss, nocturnal symptoms,
and evidence of anemia or digestive hemorrhage. Patients
with dyspepsia benefit from the endoscopy, because this has
proved to reduce anxiety rates by ruling out cancer or a
peptic ulcer.
c. Avoid alcohol, tobacco and non-steroidal
anti-inflammatory drug (NSAIDs)
These are unarguably dyspepsia generators and are associated with peptic ulcers. We suggest avoiding them due to
their GI toxicity.
d.Psychoeducation and psychotherapy
Prevalence of depression and especially of anxiety is high in
patients with dyspepsia. It is important to detect such diseases and treat them, since these may increase the perception of symptoms. In our experience, symptoms such as
nausea are associated independently with anxiety and the
* Corresponding author: Gastroenterology and Digestive Endoscopy Service, Social Mexicali Hospital. 1300 Francisco Sarabia Street, Zacatecas, Z.P. 21070, Mexicali, B. C., Mexico. E-mail address: [email protected] (Á. R. Flores-Rendón).
Managing functional dyspepsia
147
degree of anxiety is positively correlated with the intensity
of the symptoms.2
We strongly recommend the use of tools like the in Hospital Anxiety and Depression Scale survey (validated in Mexico) as well as the Rome Psychosocial Alarm survey for
anxiety and depression detection in patients with dyspepsia.
Pharmacological measures
Finding pharmacological measures that function better than
the placebo is definitely a hard task in functional disorders,
because placebos have a very high effect to control dyspepsia, from 30% up to 70%. In case of functional dyspepsia we
must remember that we are dealing with 2 diseases instead
of just one (epigastric pain and postprandial discomfort),
which may coexist. Thus, we must examine patients for the
presence of each and every one of the symptoms, which will
tell us the pathophysiological aspect involved, and enable
us to treat the patient based or their symptoms. Most of
the published clinical trials about functional dyspepsia
treatment evaluate for both types of dyspepsia; hence, the
results must be carefully interpreted. The efficacy of different pharmacological treatments for functional dyspepsia is
variable (Table 1).
Available pharmacological treatments for
dyspepsia:
• H. pylori eradication treatment: One of the
patient’s biggest fears about dyspepsia is having H.
pylori, the patients show a major concern caused
by a microorganism, which may have been in their
stomachs for a long time already. Eradication
treatment has an effectiveness measured as a
number needed to treat (NNT) of 14, which in specialty care is not too effective. Nevertheless, a
recent clinical trial shows that it is a good strategy
in primary care medicine as well as in places of
high prevalence like our county. Some patients benefited by this treatment are those who manifest
pain.
• Anti-secretory drugs: Both type-2 anti-histaminergic pharmaceuticals (i. e. ranitidine) as well as
Table 1 Efficacy of pharmacological treatments for
functional dyspepsia.
Studies
Points
NNT (95% CI)
Tricyclics
Treatment
4
167
2 (1.5-5)
Prokinetics
17
4,495
5 (3-11)
Anti-H2
11
2,164
8 (5-24)
PPI
13
5,660
9 (6-19)
H. pylori
eradication
21
4,331
14 (10-20)
NNT: needed to treat; CI: confidence interval; PPI: proton pump
inhibitor; H. pylori: Helicobacter pylori.
proton pump inhibitors are medications of moderate efficacy with an NNT of 8 and 9, respectively.
Patients who may be benefited by the use of these
medications are those with burning pain, overlapping with gastroesophageal reflux (frequent in our
population, up to 50%). However, it is important to
know that the patients who benefit the least are
those with postprandial distress, considering that
gastric emptying studies have proven that proton
pump inhibitor (PPI) reduces solids rate and this
could worsen the symptoms.
• Prokinetics: These are useful medications in the
treatment of postprandial distress syndrome;
however researchers in US forget them because its
therapeutic dosage approaches the level of dosage
which causes adverse effects. Nevertheless, when
these are used wisely, it gives dyspepsia patients a
major benefit with an NNT of 5. It is important to
highlight that there is a considerable amount of
prokinetics available in Mexico, but we must chose
the one that, in addition to being effective, has an
acceptable safety profile.
• Antidepressants: Highly effective medications in
the treatment of dyspepsia since they work as visceral analgesics. It is important to highlight that
the use of these medications is for pain management. However, we must evaluate the presence of
subjacent anxiety or depression for their treatment.3
Selective serotonin receptor inhibitors have only
proved to have a positive effect over quality of life
but not in pain. A recent study showed preliminary
results demonstrating that amitriptyline is better
than a placebo for dyspepsia management, yet not
escitalopram. Tricyclic antidepressants are modulators of the perception of pain; their prescription
in the treatment of dyspepsia should follow the
concept of “low and slow”: effective dosages in
dyspepsia tend to be lower than those for depression and their therapeutic effects tend to be noticed sooner than in depression. This treatment’s
effectiveness is proven with an NNT of 2. It is important to consider that before the prescription of
a tricyclic, organic diseases must have been ruled
out because these medications have been demonstrated to be effective for pain management in general and it could be masking other causes. We
must emphasize and consider that if we want to
treat anxiety or depression there are other medications with better results, thus my suggestion
would be to refer to a specialist for its management and maintain the tricyclic’s minimum effective dosage. Recent studies have demonstrated that
amitriptyline can manage pain, as well as nausea4
(regardless of the fact that one of its effects is to
delay gastric emptying) and even can be found in
the American College of Gastroenterology gastroparesis management guide because of its effect
over this problematic symptom.
Regarding dyspepsia treatment duration the suggestion is
3 months; however, the use of tricyclic as an option can be
considered up to 6 months (there is not a well-established
time).
148
Functional dyspepsia is more complex than we think and
therapeutic development seems to be stagnant for some
years now. Management guidelines are different based on
prokinetic availability; always consider H. pylori eradication
as a first choice. They suggest subdividing the patient into 2
groups (epigastric pain or postprandial distress); however, it
is very frequent that the patient suffers both (up to 50%).
Therefore my recommendation is to consider the fact that
symptoms are the key to establishing a treatment plan, because they can explain whether the patient is hypersensitive and requires a tricyclic, if the patient has gastric
relaxation or emptying issues where a prokinetic would be
ideal, or if acid is casual and an anti-secretor would be the
best option. Even though we must consider that the best
option is probably the combination of 2 or more medications
based on the symptoms.
Á. R. Flores-Rendón
References
1. Tack J, Talley N. Functional dyspepsia-symptoms, definitions
and validity of the Rome III criteria. Nat Rev Gastroenterol Hepatol 2013;10:134–141.
2. Flores Rendón AR, Ramos B, Durán Arizaga HJ, et al. The Relation of Anxiety and Digestive Symptoms in Uninvestigated Dyspepsia: A Different Look on Troublesome Symptoms. Gastroenterology 2013;144(suppl1):S683.
3. Mak AD, Wu JC, Chan Y, et al. Dyspepsia is strongly associated
with major depression and generalised anxiety disorder - a
community study. Aliment Pharmacol Ther 2012;36:800-810.
4. Braak B, Klooker TK, Wouters MM, et al. Randomised clinical
trial: the effects of amitriptyline on drinking capacity and
symptoms in patients with functional dyspepsia, a double-blind
placebo-controlled study. Aliment Pharmacol Ther 2011;34:638–
648.
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Copia de título, o carta de pasante o de servicio
social (uno de estos tres docuemntos).
Copia e CURP (extranjeros pasaporte).
Copia de Kárdex completo.
1 Fotografía tamaño infantil a color.
Utilización del Sistema de Respuesta Inmediata
de la Audiencia (SIRIA) como una herramienta
para interactuar continuamente con los
asistentes y mejorar su aprendizaje.
Incluimos los libros “Fundamentos para el
Ejercicio de la Medicina” y el “Cuaderno de
Trabajo Fundamentos para el Ejercicio de la
Medicina” que contienen más de 200 casos
clínicos y 300 temas de salud.
Enviar digitalizados estos documentos a: [email protected]
PRECIO: Del 1 de septiembre de 2014 al 31 de
enero de 2015.................................. $ 18,000.00
1 de febrero al 30 de marzo.............. $ 19,500.00
1 de abril al 31 de mayo.................... $ 20,500.00
Del 1 de junio en adelante................. $ 22,000.00
El temario del
curso NO esta
basado en el contenido
del libro, sino que se
complementan.
Practica para el ENARM con nuestro
“Simulador de Examen de Residencias
Médicas (SERM)” a través de nuestro portal de
internet: www.meduconuanl.com.mx
NO hay reembolso por cancelación.
Aplicación de exámenes de evaluación durante
el curso.
Constancia de asistencia al curso con un valor
curricular por más de 200 horas de educación
continua.
Se incluye el servicio de comida para todos los
asistentes al curso, así como servicio de café
durante el día.
Centro Regional de Información y Documentación en Salud “Dr. Alfredo
Piñeyro López” planta baja. Av. Francisco I. Madero y Dr. Eduardo
Aguirre Pequeño Col. Mitras Centro Monterrey, N.L. Número de Cuenta
Banorte: 0168442120 Clabe interbancaria: 072580001684421206
De nuestros asistentes son
seleccionados para realizar
su residencia médica.

journal of science and research - Facultad de Medicina de la UANL

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