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

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Vol. 16 • Num. 63 • April-June 2014
Vol. 16 • Num. 63 • April-June 2014 • ISSN 1665-5796
JOURNAL OF SCIENCE AND RESEARCH
SCHOOL OF MEDICINE AND “DR. JOSÉ ELEUTERIO GONZÁLEZ” UNIVERSITY HOSPITAL
UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN
OLFACTORY DYSFUNCTION
in young smokers
TERMINAL INTERRUPTION
of reflux source technique
in the treatment of
active venous ulcers
MEDICINA UNIVERSITARIA
SMOKING, DEPRESSION,
and suicide risk in
the nursing staff
of a Third-Level Hospital
www.elsevier.es
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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
Monterrey, México
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 63, abril-junio de 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.
Editada por: Masson Doyma México, S.A. Av. Insurgentes Sur 1388, Piso 8, Col. Actipan Del. Benito Juárez, CP 03230, México, D.F. Tels.: 5524-1069, 5524-4920, Fax: 5524-0468.
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Delegación Benito Juárez, México D.F. Este número se terminó de imprimir en junio de 2014 con un tiraje de 1,200 ejemplares. Índices en los que aparece esta revista: ARTEMISA
(Artículos Editados en México sobre información en Salud). En Internet, compilada en el Índice Mexicano de Revistas Biomédicas (IMBIOMED) y LATINDEX.
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Contents
EDITORIAL
Volume 16
Issue 63
April-June 2014
45 The value of personal experience in academic medicine
D. Gómez-Almaguer
ORIGINAL ARTICLES
46 Olfactory dysfunction in young smokers
J. A. Morales-del Ángel, J. L. Treviño-González, B. González-Andrade, R.
Santos-Lartigue, V. J. Villagómez-Ortiz, M. J. Jr. Villegas-González
49 Similarities between the lipid profile of Mexican patients with lupus and the
general population
I. J. Colunga-Pedraza, D. Á. Galarza-Delgado, F. Góngora-Rivera, J. A. Esquivel-Valerio, R. A. Carrillo-Palacios, S. Segarra-Linares, A. L. Sánchez-Núñez,
P. R. Colunga-Pedraza, D. Vega-Morales, M. A. Garza-Elizondo
54 Terminal interruption of reflux source technique in the treatment of active
venous ulcers
O. F. López-Lugo, R. Salinas-Domínguez, J. A. Tamez-del Bosque, G. E. MuñozMaldonado
60 Smoking, depression, and suicide risk in the nursing staff of a Third-Level
Hospital
R. A. Sánchez-Núñez, C. Ramírez, M. V. Gómez-Meza
66 Effects of liraglutide on weight reduction and metabolic parameters in obese
patients with and without type 2 diabetes mellitus
E. A. García-Cantú, H. H. Alvarado-Saldaña, H. E. Támez-Pérez, G. Rubio-Aguilar
scientific LETTERS
71 Dyke-Davidoff-Masson syndrome: A case study
M. A. Duncan, S. Vázquez-Flores, E. B. Chávez-Lluévanos, A. C. Cantú-Salinas, L.
de León-Flores, H. J. Villarreal-Velázquez
74 Caudal regression syndrome: A case report
M. A. Duncan, A. C. Cantú-Salinas, D. L. Villarreal-Rodríguez, C. Muñiz-Landeros, H. J. Villarreal-Velázquez
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REVIEW ARTICLE
78 Review of plants with hepatoprotective activity evaluated in Mexico
L. Torres-González, N. Waksman-de Torres, J. Pérez-Meseguer, L. Muñoz-Espinosa, R. Salazar-Aranda, P. Cordero-Pérez
EXPERT’S CORNER: A PERSONAL APPROACH
87 Fear of the unknown: Influenza vaccination
J. G. Velasco-Castañón, C. E. Medina-De la Garza
VOICES OF DOCTORS AND PATIENTS
90 Between the rose and the shoulders of giants
R. Garza-Mercado
96 The excluded
M. Granados-Shiroma
SPECIAL ARTICLES
99 Biobanks: Experience of the School of Medicine and the “Dr. José Eleuterio
González” University Hospital of the Universidad Autónoma de Nuevo León
M. L. Garza-Rodríguez, J. A. I. Ascacio-Martínez, A. A. Pérez-Maya, D. C.
Pérez-Ibave, D. E. Monsiváis-Ovalle, H. A. Barrera-Saldaña
102The Anatomy Research Group (GIA) 10 years after its founding: Past, present
and future
R. Morales-Avalos, R. E. Elizondo-Omaña, S. Guzmán-López
Medicina Universitaria 2014;16(63):45
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Editorial
The value of personal experience in academic medicine
In today’s scientific world, there is a requirement for studies to be controlled, randomized, “blinded”, etc. for
small, medium or major decision-making, nearly at the risk
of being excommunicated or even worse. This is a world full of
guidelines, consensus, and the information of “evidencebased medicine”. Thus, we wonder if there is still a place
for the voice of personal experience, or the existence of an
“expert” in medicine.
Young scientists in the health field quickly search for data
on their smartphones or computers and may obtain objective data, generally from sources originating in the developed
world. This will occasionally go against the word of an experienced doctor, who suggests a particular action. Dogma and
autocracy are outdated and out of context, which is reasonable and logical; nevertheless, taking this practice to the
extreme can mechanize medicine and paradoxically make it
more complicated and sometimes more costly, and not necessarily more beneficial to the patient. This is particularly
important in countries like ours with significant economic
restraints.
If everything must be based on evidence, guides and consensus, what will happen to the innovative and revolutionary ideas, the audacity and art which in my opinion every
doctor should try to find in his day-to-day practice. That is
why Medicina Universitaria has created a space so that doctors with experience in a specific field and academic practice can elaborate on short topics related to their area of
influence, without the pressure of having to follow a certain
tendency or guideline; in other words, for them to tell us
their personal opinion, more in the sense of the now-called
“personalized medicine”, rather than following consensus
and guides. For this reason, starting with this issue we have
included a section called: “Expert Corner: A Personal Approach” in which each guest writer will have between 15002000 words to offer us his personal ideas and recommendations
about a specific scientific topic.
Medicina Universitaria will continue supporting studies
with the highest quality, which follow a strict rigorous scientific method and are based on the best evidence. There is no
cause for confusion, we are simply welcoming the personal
opinions of experienced doctors, scientists and scholars
with a University spirit.
D. Gómez-Almaguer, MD*
Editor
* Corresponding author: Service of Hematology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León.
Francisco I. Madero and Avenida Gonzalitos, Mitras Centro, Z.P. 64460, Monterrey, N. L. Mexico. Telephone: (+52 81) 8348 8510. E-mail address: [email protected] (D. Gómez-Almaguer).
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados.
Medicina Universitaria 2014;16(63):46-48
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Original article
Olfactory dysfunction in young smokers
J. A. Morales-del Ángel, J. L. Treviño-González, B. González-Andrade, R. SantosLartigue*, V. J. Villagómez-Ortiz, M. J. Jr. Villegas-González
Department of Otolaryngology and Head and Neck Surgery, “Dr. José Eleuterio González” University Hospital, Monterrey,
N. L., Mexico
Received: March 2013; Accepted: January 2014
KEYWORDS
Pocket Smell Test;
Olfaction; Mexico.
Abstract
Objective: To establish the prevalence of olfactory dysfunction in smoking and non-smoking
students of our Faculty who attend the Department of Otolaryngology (ENT) of our Hospital.
Materials and method: Students (smokers and non-smokers) that do and do not suffer from olfactory dysfunction. We applied a questionnaire and a pocket smell test for screening all of the
students.
Results: We evaluated 207 students, between 18 and 30 years old; 50.7% (n=105) were women
and 49.3% (n=102) were men. The smokers among them smoked up to 6 packs per year. One
hundred twenty three students were non-smokers and 84 students were smokers. Of the 84
students who were smokers, 67 (79.7%) answered the Pocket Smell Test correctly (3/3) and 17
(20.2%) students had one or more errors. We had 123 non-smoker students and 103 (83.7%) students answered the Pocket Smell Test correctly and 20 (16.2%) answered with one or more
errors. The prevalence of olfactory dysfunction in young smokers with a 95% confidence interval
would be 32.8%.
Conclusions: This study informed us about olfactory dysfunctions in our student population and
their smoking habits. We corroborate that the Pocket Smell Test is reliable with the questionnaire; nevertheless it is a screening test. We have a population of young people who smoke one
cigarette per day and who didn’t have a significant alteration in their ability of smell at the time
of the study. This is consistent with medical literature. More studies should be conducted in
order to expand this information.
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos
los derechos reservados.
* Corresponding author: Department of Otolaryngology and Head and Neck Surgery, “Dr. José Eleuterio González” University Hospital.
Francisco I. Madero and Avenida Gonzalitos, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: (+52) (81) 8333 2917. Fax: (+52)
(81) 8333 2917. E-mail address: [email protected] (R. Santos-Lartigue).
Olfactory dysfunction in young smokers
47
Introduction
Smoking is one of the most harmful epidemics the world has
seen. Over 6 million people die every year due to tobaccoconsumption related diseases. In addition, smoking is a major cause of respiratory morbidity, including medical
conditions which affect the nose.1 However, few studies
have evaluated the relationship between tobacco smoke exposure and the generation of olfactory dysfunction.2
In the olfactory process there is a chemoreceptor system
intimately related with emotions and the limbic system.
This system regulates nutrition and the sense of well-being.3
Olfactory sensitivity depends on age and gender, among
other factors. Women are superior in every aspect of the
olfactory function.4 The 4 main causes of olfactory disorders
are: trauma, viral infections, nasal causes (e.g., chronic rhinosinusitis and septal deviation) and those related to aging
and neurological conditions.5,6
The objective evaluation of the sense of smell can be performed through odor recognition tests (ORT). In the United
States, the most utilized test is the one created by the University of Pennsylvania (Smell Identification Test, Sensonics
Inc. Haddon Heights, NJ, USA). This is a “scratch and sniff”
test which includes 40 odors, and has been validated with a
high reproducibility throughout different populations. Additionally, it is a cheap, easy to use test.7 The objective of this
study was to establish the prevalence of olfactory dysfunction in medical students and to evaluate its association
with tobacco consumption.
Materials and method
We randomly included 207 students from the Faculty of Medicine of the Autonomous University of Nuevo León (UANL),
México, between 18 and 32 years of age. These students
agreed to participate in the study during the course of their
rotation in the Otorhinolaryngology Department of the “Dr.
José Eleuterio González” University Hospital. Pregnant women were excluded.
We registered the project and it was approved by the
institution’s ethics committee. All the subjects were administered a questionnaire of 10 questions followed by a
“scratch and smell” type test consisting of 3 items.
Those who denied having ever smoked answered only the
questions related to the perception of their olfaction, and if
they considered it to be diminished. Those students who
were smokers were asked to specify the number of packs/
year and type of cigarettes that they usually smoked. Sample size was determined considering a finite population of
1,600 students annually, with a reliability of 95%, a maximum variability of smoking possibilities of 50% and a maximum accepted error of 10%.
The Smell Identification Test (Sensonics Inc. Haddon
Heights, NJ, USA), is a 3-item “scratch and sniff” strip olfactory test. This test was utilized for screening all participants
in the study. Each participant was given a brochure containing 3 areas with a different smell each. Participants scratched each of these areas with a pencil, placed it under their
nose and marked the perceived smell out of 3 possible options.
We eliminated the cases where the students did not fully
complete the questionnaire, or did not participate in the
olfactory strip test.
We analyzed the data obtained using IBM SPSS® Statistics
version 20.0.0. The results derived from the descriptive statistics analysis were expressed in percentages with the use
of charts. We crossed variables performing the hypothesis
test using chi2 test.
Results
Out of the 207 evaluated students, 50.7% were female, and
59% of the students denied being a smoker. From the 84
students who were smokers, 67 answered the Olfactory Strip Test correctly (3 out of 3), while 17 had 2 correct
answers or less. On the other hand, in the non-smokers
group, 103 students answered the test correctly (3 out of 3)
and the remaining 20 obtained 2 correct answers or less (Table 1).
However, when we asked students if they could perceive any abnormality in their olfaction, 81.6% answered “no”
and 18.4% answered “yes”. In regard to whether or not they
felt any discomfort in their olfaction, 106 students said
“no”, and 101 students said “yes”; 79 students did not attribute it to any cause, 36 students attributed such to allergies
and 92 students believed it was caused by upper airway
Table 1 Relation between a background of smoking and the correct identification of the 3 smells in the olfactory test.
Smoking status
Smoker
Normal
Hits
Dysfunction
Total
Non-smoker
Total
Students (N)
67
103
170
Smokers (%)
79.8%
83.7%
82.1%
Students (N)
17
20
37
Smokers (%)
20.2%
16.3%
17.9%
Students (N)
84
123
207
Smokers (%)
100%
100%
100%
48
infections. Out of the total of the students, 76 claimed to
smoke one cigarette a day, 8 students more than one cigarette a day and 123 students said they did not smoke any
cigarettes a day. All the smokers smoked filtered cigarettes.
The prevalence of young adults who smoke and have olfactory dysfunctions is 32.8% with a 95% confidence level.
Discussion
In the United States, olfactory dysfunction is a major health
problem, with a reported prevalence of 24.5% in people older than 53 years and up to 62.5% in people older than 80.8
The etiology is multiple and the main causes include cranioencephalic trauma, upper airway infections and nasosinusal affection.9
Smoking contributes to the development of diverse disorders which affect the airways, oral cavity and other organs.10 However, the relationship between smoking and the
olfactory function is poorly known. 11 Bramerson studied
1,387 patients in Switzerland, finding a prevalence of olfactory dysfunction of 19.1% with a statistically significant relationship between age, gender and nasal polyposis with the
loss of sense of smell without finding a relationship with
smoking.12
We investigated the amount of tobacco consumed among
a young population, and its relationship with olfactory dysfunction. From the 207 students, 81.6% did not show abnormalities in their olfaction during the questionnaire and after
the test 82.1% showed results indicating normal olfaction.
Out of the total of the population, 40.6% presented a positive smoking background a 20.2% abnormality in the tests
within this group. Compared to 16.3% abnormality in the
non-smokers, we observed that there was no significant difference between both groups. With these results, we find
that our study is very similar to the data found in medical
literature.
In addition, we found that upper airway infections are a
frequent cause of olfactory dysfunction, in contrast to the
findings by Bramerson where the predisposing factors were
age, gender and nasal polyposis.
In spite of the use of olfactory strips, the study is considered to be scrutinizing; the results were properly correlated
with the data found in the questionnaires, facilitating the
approach to this special sense which is the sense of smell.
J. A. Morales-del Ángel et al
Conclusion
This study allowed us to learn more about our student population, as well as their smoking habits. We conclude that,
just as reported in medical literature, we did not find a significant association between smoking and olfactory dysfunction. At the same time, we found that upper airway
infections are a significant cause for such dysfunction.
Conflicts of interest
The authors have no conflicts of interest to declare.
Funding
No financial support was provided.
References
1. Accesed in April 2014.http://www.who.int/mediacentre/factsheets/fs339/en/index.html
2. Lalwani AK. Current Diagnosis & Treatment, Otolaryngology
Head and Neck Surgery. 2nd edition. USA: McGraw Hill; 2008.
3. Doty RL, Shaman P, Kimmelman CP, et al. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory
function test for the clinic. Laryngoscope 1984;94:176-178.
4. Pinto MJ. Olfaction. Proc Am Thorac Soc 2011;8:46-52.
5. Sikorska-Jaroszyńska MHJ, Mielnik-Błaszczak M, Krawczyk D, et
al. Passive smoking as an environmental health risk factor. Ann
Agric Environ Med 2012;19:547-550.
6. Holbrook EH, Leopold DA. An updated review of clinical olfaction. Curr Opin Otolaryngol Head Neck Surg 2006;14:23-28.
7. Cummings Otolaryngology: Head & Neck Surgery. 4th ed. USA:
Mosby; 2005.
8. Landis BN, Konnerth CG, Hummel T. A study on the frequency of
olfactory dysfunction. Laryngoscope 2004;114:1764-1769.
9. Pause BM. Processing of body odor signals by the human brain.
Chemosens Percept 2012;5:55-63.
10. Spinella M. A relationship between smell identification and empathy. Int J Neurosci 2002;112:605-612.
11. Vennemann MM, Hummel T, Berger K. The association between
smoking and smell and taste impairment in the general population. J Neurol 2008;255:1121-1126.
12. Bramerson A, Johansson L, Ek L, et al. Prevalence of olfactory
dysfunction: the skovde population-based study. Laryngoscope
2004;114:733-737.
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Original article
Similarities between the lipid profile of Mexican patients with
lupus and the general population
I. J. Colunga-Pedrazaa,*, D. Á. Galarza-Delgadoa,b, F. Góngora-Riverac, J. A. EsquivelValerioa, R. A. Carrillo-Palaciosd, S. Segarra-Linaresd, A. L. Sánchez-Núñezd, P. R.
Colunga-Pedrazab, D. Vega-Moralesa, M. A. Garza-Elizondoa
a
Service of Rheumatology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Monterrey, N. L., Mexico
Department of Internal Medicine, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo
León, Monterrey, N. L., Mexico
b
Service of Neurology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
c
d
Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: October 2013; Accepted: January 2014
KEYWORDS
Lipids; Systemic lupus
erythematosus;
Atherosclerosis; Risk
factors; Mexico.
Abstract
Introduction: Premature cardiovascular events have been observed in systemic lupus erythematosus (SLE) patients, but the reason for this accelerated process is still debatable; although
traditional risk factors are more prevalent in such patients than in the general population, they
do not seem to fully explain that enhanced risk. One of the most important conditions is a proatherogenic lipid profile. There is not enough data about it in Mexican SLE patients.
Objective: To establish the differences in the lipid profiles between Mexican patients with SLE
and the general population.
Material and methods: Observational, transversal, descriptive and comparative study, between
SLE patients and age-sex-matched healthy volunteers. We performed a full lipid profile (by
spectrophotometry) 14 hours of fast. The results obtained were analyzed by the statistical program SPSS® Statistics version 17.
Results: We studied the full lipid profiles of 138 subjects, 69 with a diagnosis of SLE and 69 agesex-matched healthy volunteers; 95.7% were females and 4.3% males. Average age was 30 years;
average body mass index (BMI) 25.96 ± 5.96 kg/m² in SLE patients and 26.72 ± 4.36 kg/m² in the
control group (p = 0.396). Average of total cholesterol 156 mg/dl in the SLE patients and 169.4
mg/dl in the control group (p = 0.028); average of low density lipoprotein (LDL) cholesterol
* Corresponding author: “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León. Gonzalitos 235 North
Avenue, Mitras Centro, Z.P. 64020, Monterrey, N. L., Mexico. Telephone: (+52) (81) 8348 2015. Fax: (+52) (81) 8348 2065. E-mail address:
[email protected] (I. J. Colunga-Pedraza).
50
I. J. Colunga-Pedraza et al
85.27 mg/dl in the SLE patients and 97.57 mg/dl in the control group (p = 0.023).
Conclusions: We did not find statistical differences in the lipid profiles among patients and
healthy volunteers, which could explain increased cardiovascular morbidity and mortality observed in SLE patients.
Introduction
Premature cardiovascular events have been observed in systemic lupus erythematosus (SLE) patients, but the reason
for this accelerated process is still debatable.1
In addition to traditional cardiovascular risk factors in SLE
patients, there are factors inherent to the disease such as:
immune complex-induced endothelial damage, vasculitis,
thrombosis associated with antiphospholipid antibodies, Libman Sacks´ endocarditis, renovascular hypertension, glomerulonephritis and corticosteroid therapy used as part of
the disease treatment.1
A greater prevalence of dyslipidemia has been reported in
these patients, finding a marked pro-atherogenic lipid profile, i.e., elevation low density lipoprotein (LDL), lipoprotein
(a), triglycerides and free fatty acids, as well as reduction of
high density lipoproteins (HDL).2 Amongst traditional cardiovascular risk factors, dyslipidemia is considered to represent a
greater impact on the development of cardiovascular disease, in addition to being related to a higher renal morbidity
and a higher mortality in SLE patients.3
Chronic use of glucocorticoids, as part of the treatment
of this pathology, also favours the development of a proatherogenic lipid profile in this population. Additionally, frequently used immunosuppressants for SLE treatment positively correlate with the antioxidant and antiinflammatory
ability, reporting an oxidized LDL reduction (LDLox) in patients who receive them.4
About 75% of SLE patients develop hypercholesterolemia 3
years after diagnosis; these patients report the highest rates of cardiovascular events.5 In patients with more than
5-year of diagnosis progression, the risk of acute myocardial
infarction has been reported to increase up to 52 times.6
For the above mentioned reasons, we decided to analyze
and establish the differences in the lipid profiles between
Mexican patients with SLE and the general population, matched by age and gender.
Material and methods
We performed an observational, transversal, descriptive
and comparative study. We included 69 patients diagnosed
with SLE by a rheumatologist, meeting at least 4 classification criteria of the American College of Rheumatology, modified in 1997.7 The patients were 18 years of age or older,
had no known cardiovascular history (myocardial infarction,
angina, stroke, transient ischemic attack), attended by a
rheumatologist in “Dr. José Eleuterio González” University
Hospital and agreed to participate through a signed informed consent. This study was approved by our local Ethics
Committee (MI09-007).
Subsequently, the patients were matched with 69 healthy
volunteers by age and gender; subjects without any autoimmune diseases and no known cardiovascular pathologies at
the randomization. All subjects (138) were required to comply with a 14-hour fast, following which a venipuncture
was performed to obtain a full lipid profile, using the spectrophotometry technique. In addition, the following tests
were done: erythrocyte sedimentation rate using the Wintrobe method, ultra-sensitive C-reactive protein (CRP),
Complete Blood Count in the same lab.
We compared the total cholesterol value, LDL, HDL and
triglycerides; then, we identified pro-atherogenic characteristics in the lipid profile, establishing as a cut-off point in
accordance with that described in the literature as a cardiovascular risk factor: total cholesterol > 200 mg/dl, triglycerides > 150 mg/dl, HDL < 45 mg/dl, LDL > 100 mg/dl. We
obtained the BMI of all patients.
Results were analyzed using the statistical program SPSS
v17, performing a descriptive analysis for demographic and
clinical variables.
For the binominal variable contrast, we used chi-square
test or Fisher’s exact test, with 2 x 2 contingency tables; for
non-parametric variables we used the Mann-Whitney U test.
p ≤ 0.05 was taken as a significant value.
Results
We analyzed 69 SLE patients and 69 healthy patients, 66
women (95.7%) and 3 men (4.7%) in each group matched by
sex and age, with a median age of 30 years, and an interquartile range of 14 (Table 1).
In the lipid profile, we found a total cholesterol average
of 156 mg/dl in the group of SLE patients compared to 169.4
mg/dl in the control group (p = 0.028). The higher mean is
in the group of healthy individuals, with a statistically significant difference. As far as LDL cholesterol levels, we found
an average of 85.27 mg/dl in the group of SLE patients while
in the group of healthy subjects the mean was 97.57 mg/dl
(p = 0.023), also with a statistically significant difference.
Despite finding statistically significant differences for absolute figures of total cholesterol and LDL cholesterol; when
we performed the analysis for pro-atherogenic characteristics we did not find any statistically significant differences
between both groups (Table 2).
In addition, we analyzed other clinical and biochemical
parameters (BMI, erythrocyte sedimentation rate, albumin,
CRP, uric acid, glucose and hemoglobin), finding that data in
the group of patients regarding the erythrocyte sedimentation rate, CRP and serum creatinine were higher with statistical significance. On the other hand, the healthy volunteers
Similarities between the lipid profile of Mexican patients with lupus and the general population
51
Table 1 Clinical characteristics of the studied population. Monterrey, N. L., Mexico, 2011.
Characteristic
Gender
• Male n (%)
• Female n (%)
Median age in years (interquartile range)
SLE
Volunteers
p
3 (4.3)
66 (95.7)
3 (4.3)
66 (95.7)
1.000
30 (14.0)
30 (14.0)
1.000
Framingham’s Score ± SD
1.63 ± 1.48
1.43 ± 0.977
0.771
Body mass index ± SD
25.96 ± 5.93
26.72 ± 4.36
0.396
SD: standard deviation; SLE: systemic lupus erythematosus.
group had higher hemoglobin, lymphocytes, platelets, albumin and glucose, also with statistical significance (Table
2).
In the 69 SLE patients, we also analyzed the disease’s characteristics; finding that the average number of years of SLE
diagnosis at the time of entering the study was 5 years; with
an interquartile range of 8, this population had an average
diagnostic age of 25.8 ± 7.41 years. The disease activity index used was the MEX-SLEDAI, finding an average of 1.69 ±
2.71, which places the average of the population in the low
activity group.
Concerning medication use, we found that 68 patients
(97.1%) used antimalarials at the time of the study; 20 patients (29.4%) were taking chloroquine at an average dosage
of 150 mg/day, while 48 patients (70.5%) were taking hydroxychloroquine at an average dosage of 200 mg/day. Sixty
patients (88.2%) had been taking antimalarials routinely for
over a year.
Discussion
We found the difference in total cholesterol and LDL averages to be statistically significant; however, it was significantly greater in the healthy group, which may be explained
by the genetics that our Mexican population carries for dyslipidemia. Thus, we compared BMI between both groups and
lipid profiles, finding no statistically significant differences.
When we analyzed atherogenic lipid levels, thus identifying
cardiovascular risk, we found no differences between the lipid profiles from the SLE patients and the healthy volunteers.
This suggests that there may be qualitative differences rather
than quantitative ones in lipids of SLE patients.
In SLE patients, an increase in hydroperoxidized lipids associated with endothelial dysfunction has been reported, as
well as a decrease in antioxidizing ability.8 High oxidized
HDL levels (HDLox), not only eliminate the protecting effect
of HDL, but also are associated with pro-inflammatory action and accelerated atherogenesis.2 IgG-type antibodies
against LDLox are also linked with the early development of
atherosclerosis observed in SLE patients.8
One of the weaknesses in our work is the fact that we did
not measure LDLox levels. Increased cardiovascular risk,
which in recent years has been found in SLE patients, in this
studied population is not consistent with a pro-atherogenic
lipid profile; however, further studies including larger number of patients are required to determine the causes that
lead to an increase in cardiovascular morbimortality in this
specific population.
In our Mexican population with SLE, we were not able to
find a marked atherogenic profile, contrary with the recent
published.3 However, in this last publication they studied
Caucasian, Black and Asian races but did not include the
Latin American population. Additionally, in this group characteristics associated with total cholesterol increase were
age over 30 years and use of prednisone, with dosages greater than 10 mg/day. In the population studied by Petri et
al., 35% of the patients used hydroxichloroquine on a regular basis, unlike our population in which 97.1% were taking
anti-malarials. This is relevant because the use of hydroxychloroquine has been linked to an improvement in lipid
profiles of SLE patients.9
In a study performed in India including 30 SLE patients
paired by sex and age with 30 control subjects, dyslipidemia was found in 63% of SLE patients; however, a statistically significant difference was only found in triglycerides,
which turned out to be greater in the SLE group.10 In the
same study, 63% of SLE patients had been diagnosed with
lupus nephropathy, which could have altered lipid characteristics in that population in contrast with our population,
in which they found only 12% of lupus nephropathy (none
with proteinuria in nephrotic range nor undergoing renal
replacement therapy, when subjects were included in the
study).
In a trial including Mexican subjects, in which 16 SLE patients were studied, no difference was found in the lipid
profile of SLE patients, compared to a healthy control
group, paired by age, sex and BMI. However, one advantage
of our study was that did include a larger number of patients and controls.11
The few studies performed in a Mexican population regarding the lipid profile in SLE patients, make it indispensable
to conduct further studies on the issue. The differences
found about hemoglobin, erythrocite sedimentation rate,
albumin, CRP, albumin, creatinine, platelets and lymphocytes, may be explained as expected changes in SLE patients.
Another important consideration is that the SLE patient
sample had a low MEX-SLEDAI (under 2, on average), which
places them in the subgroup of low-activity patients, the
disease activity being another variable frequently associated with accelerated atherosclerosis; however, in our population did not keep a relationship with the disease activity.12
52
I. J. Colunga-Pedraza et al
Table 2 Comparison between the lipid profile and biochemical parameters of patients with SLE and healthy volunteers, of the
same age and gender. Monterrey, N. L., Mexico, 2011.
SLE
Volunteers
p
Total cholesterol (mg/dl), mean ± SD
156.13 ± 36.45
169.4 ± 33.7
0.028
VLDL (mg/dl), mean ± SD
26.25 ± 17.93
22.9 ± 10.77
0.186
LDL (mg/dl), mean ± SD
85.27 ± 31.89
97.57 ± 30.85
0.023
HDL (mg/dl), mean ± SD
44.09 ± 12.65
47.01 ± 8.97
0.119
Triglycerides (mg/dl),
mean (IR)
103 (107)
110 (79)
0.767
LDL > 100 mg/dl, n (%)
21 (30.43)
29 (42.02)
0.214
HDL < 45 mg/dl, n (%)
42 (60.86)
33 (47.82)
0.171
Triglycerides > 150 mg/dl, n (%)
23 (33.33)
20 (28.98)
0.713
Total cholesterol > 200 mg/dl, n (%)
10 (14.49)
11 (15.94)
1.000
12.25 ± 1.63
13.21 ± 0.96
< 0.001
6198.4 ± 2444.4
6819.13 ± 1450.2
0.212
Parameter
Hemoglobin (g/dl),
mean ± SD
Leukocytes (cels/mm3), mean ± SD
Platelets (10 /mm ), mean ± SD
287.3 ± 99.9
309.4 ± 62.8
0.015
Albumin (mg/dl), mean ± SD
3.61 ± 0.40
3.84 ± 0.247
< 0.001
(ESR) (mm/h), mean ± SD
25.0 ± 15.75
18.79 ± 9.67
0.006
Lymphocytes (10 /mm ), mean ± SD
1.5 ± 0.69
3.52 ± 0.6
< 0.001
Glucose (mg/dl),
mean (IR)
75 (12.0)
81.0 (11.0)
< 0.001
12 (5)
11 (3.5)
0.245
0.64(0.2)
0.59 (0.14)
0.045
4.23 ± 1.14
3.95 ± 0.901
0.236
34 (49.3)
2 (2.9%)
< 0.001
3
3
3
3
Urea nitrogen (mg/dl), mean (IR)
Creatinine (mg/dl),
median (IR)
Uric acid (mg/dl), mean ± SD
CRP positive, n (%)
SLE: systemic lupus erythematosus; LDL: low density lipoproteins; VLDL: very low density lipoproteins; HDL: high density lipoproteins;
CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; IR: interquartile rango.
As for other traditional cardiovascular risk factors (obesity, hypertension, hyperglycemia after fasting),12 no link with
lipid profile alterations was found. However, this could be
related to our patients’ age at the time of inclusion in the
study (mean 30 years); at this age, cardiovascular comorbidities are less prevalent.
Conclusions
We did not find statistical differences in the lipid profiles
among patients and healthy volunteers to explain the increased cardiovascular morbimortality observed in SLE patients.
Funding
References
1. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional
Framingham risk factors fail to fully account for accelerated
atherosclerosis in systemic lupus erythematosus. Arthritis
Rheum 2001;44:2331-2337.
2. Thomas GN, Tam LS, Tomlinson B, et al. Accelerated atherosclerosis in patients with systemic lupus erythematosus: a review of the causes and possible prevention. Hong Kong Med
J 2002;8:26-32.
3. Petri M, Spence D, Bone LR, et al. Coronary artery disease
risk factors in the Johns Hopkins Lupus Cohort: prevalence,
recognition by patients, and preventive practices. Medicine
(Baltimore) 1992;71:291-302.
4. Leong KH, Koh ET, Feng PH, et al. Lipid profiles in patients with
systemic lupus erythematosus. J Rheumatol 1994;21:1264-1267.
5. Páramo JA, Rodríguez JA, Orbe J. Aterosclerosis en las enfermedades inflamatorias. Med Clin (Barc) 2007;128:749-756.
6. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic
lupus erythematosus: Comparison with the Framingham Study.
Am J Epidemiol 1997;145:408-415.
Similarities between the lipid profile of Mexican patients with lupus and the general population
7. Hochberg MC. Updating the American College of Rheumatology
revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
8. López LR, Salazar-Paramo M, Palafox-Sánchez C, et al. Oxidized
low-density lipoprotein and beta2-glycoprotein I in patients
with systemic lupus erythematosus and increased carotid
intima-media thickness: implications in autoimmune-mediated
atherosclerosis. Lupus 2006;15:80-86.
9. Pons-Estel GJ, Alarcón GS, Hachuel L, et al. Anti-malarials
exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a LatinAmerican cohort. Rheumatology (Oxford) 2012;51:1293-1298.
53
10. Kakati S, Doley B, Deve A, et al. Serum lipid profiles in patients
with systemic lupus erythematosus. J Indian Rheumatol Assoc
2003;11:5-7.
11. Díaz-González O, Andrade-Ortega L, Irazoque-Palazuelos F, et
al. El lupus eritematoso sistémico como factor de riesgo independiente en el desarrollo de dislipidemias. Reumatol Clin
2008;4 Supl.
12. Silvariño R, Inoue Sato E. Factores de riesgo para aterosclerosis
en enfermedades autoinmunitarias sistémicas. Rev Med Urug
2008;24:118-132.
medicina
universitaria
www.elsevier.com.mx
Original article
Terminal interruption of reflux source technique in the treatment
of active venous ulcers
O. F. López-Lugo*, R. Salinas-Domínguez, J. A. Tamez-del Bosque, G. E. MuñozMaldonado
Service of General Surgery, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Received: September 2013; Accepted: March 2014
KEYWORDS
Venous ulcers; Venous
insufficiency;
Treatment; Mexico.
Abstract
Introduction: The treatment for venous ulcers in most cases is unsatisfactory, with recurrences
and poor healing.
Objective: To evaluate adjuvant therapy in the treatment of active venous ulcers.
Methods: We analyzed 20 patients with active venous ulcers attending the General Surgery outpatient clinic at the “Dr. José Eleuterio González” University Hospital from October 2012 to
January 2013. They were randomly divided into 2 groups: Group A (11 patients) underwent
compression therapy and group B (9 patients) underwent compression therapy plus removal of
the vein that gives terminal reflux to the ulcer, guided by ultrasound (microphlebectomy). Patients were evaluated weekly (8 weeks). At each assessment, photographs and lesion measurements were taken and pain was evaluated using the visual analog scale.
Results: No significant differences were found between the study groups in terms of age,
weight, height, body mass index (BMI), ankle-brachial index, and baseline measurement of the
ulcer (p>0.05). Group B showed a greater reduction in ulcer size and a statistically significant
lower score on the visual analog pain scale (p<0.05) from the second and third week of
treatment, respectively.
Conclusions: The results obtained in patients with surgical procedure (group B) are consistent
with the reported efficacy of chronic venous ulcer treatment with saphenectomy (conventional
surgery), the difference is that in this study we used a minimally invasive procedure (microphlebectomy).
* Corresponding author: Anillo Periférico 715-4 Avenue, Colinas de San Jerónimo, Z.P. 64630, Monterrey, N. L., Mexico (O. F. López-Lugo).
Terminal interruption of reflux source technique in the treatment of active venous ulcers
Introduction
A venous ulcer is the most serious consequence of chronic
venous insufficiency. This disease has been known for over
3500 years. Nowadays, it is a pathology which draws little
attention, despite new findings regarding its pathogenesis
and treatment. In our opinion, we should focus on its healing rather than on the cause of the problem. About 1% of
the population has a history of Postphlebitic ulcers. This
percentage increases to 4% in the population over 65.1 The
Bonn Vein Study included 3072 participants, finding changes
in pigmentation or eczema in 2.9% and a postphlebitic ulcer in 0.7%.2 A multicenter study conducted in Poland with
40,085 participants found skin changes in 4.6% of the patients,
a healed ulcer in 1% and active ulcers in 0.5%.7 Heit et al.
found a venous ulcer incidence of 18 for every 100,000 people
a year and a yearly Billion-dollar expenditure on public health.3
Current theories about the etiology of severe chronic venous insufficiency are related to chronic venous hypertension.4,5 When weakness develops in the walls of the veins,
dilatation of the valve ring is produced, impeding valve
coaptation.6 Recent data indicates that venous hypertension
causes extravasation of macromolecules and erythrocytes
inside the interstitium.7,8 Erythrocytes and protein interstitial degradation are a powerful leucocyte chemoattractant.
This suggests a role in cytokines, demonstrated by the presence of beta growth factor, which may cause fibrosis by
stimulation of the extracellular matrix, reducing oxygen and
nutrient circulation thus resulting in changes in the color
and consistency of the skin.5
Advanced isolated venous insufficiency includes a sensation of excessive weight on the legs as well as edema. Signs
include a phlebostatic crown (spider-shaped outbreak consisting of small varicose intradermal veins on the medial aspect of the ankle and foot), and changes in skin such as
lipodermatosclerosis, which in its chronic phase develops
as shiny, hardened and pigmented skin.9,10 Ulcers have irregular edges with neo-epithelization with a pinkish base with
granulation tissue, on occasions with a fibrin coating. Pulse
palpation and the ankle-brachial index test are necessary in
order to rule out an arterial insufficiency.11,12 The Doppler
ultrasound is currently the gold standard in venous insufficiency diagnosis.13,14 The American Venous Forum classifies
active venous ulcers as C6.15,16
Treatment includes general measures: patient education,
weight loss, elevation of the extremity and exercise.17-20
Factors like immunosuppression, malnutrition, diabetes mellitus, arterial insufficiency, local infection, and cardiac insufficiency may affect ulcer healing. A compressive therapy
is the base in venous ulcer treatment, and this has been
validated in random studies.21
O’Meara et al. and Ukat et al., proved a statistically significant decrease in time in ulcer healing (p=0.005) with the
use of multiple elastic bandages compared to the inelastic
systems.22-24 Myers et al. found superficial venous insufficiency with Doppler ultrasound in 38% of the patients with
venous ulcers, and a combination of superficial and deep venous insufficiency in 48% of the patients with ulcers.25 A study showed venous ulcer healing in 77% of the cases 12
months after superficial venous reflux surgical treatment.26
Bush included 14 patients with chronic venous ulcers (6 to
24 months) treated with compressive therapy. The patients
55
were treated with the terminal interruption of reflux source technique guided by a Doppler ultrasound, which consisted of injecting sclerosant foam into the ulcers proximal
veins, with an ulcer healing time of 6 to 8 weeks in 11 patients, with 5 years with no recurrences in 7 patients, 2
years with no recurrences in 4 patients, a year with no recurrences in 2 patients and recurrence in one of them.27
The objective of this study is to assess the clinical benefits in reducing the size and pain in active venous ulcers
using terminal interruption of reflux source technique guided by ultrasound in the treatment of venous ulcers.
Materials and methods
We performed a prospective, comparative longitudinal study. A non-blind, experimental, controlled clinical trial.
Inclusion criteria: A C6 classification by The American Venous Forum (active venous ulcers), age of at least 18 years,
venous insufficiency diagnosed by a Doppler ultrasound, BMI
between 18.5 and 34.9, no local infection, a signed informed consent, having no previous venous surgery and an
ankle-brachial index over 0.85.
We analyzed 20 patients with a diagnosed venous ulcer in
their lower limbs, with a previously signed consent form,
attending the General Surgery outpatient clinic at the “Dr.
José Eleuterio González” University Hospital, and meeting
the inclusion criteria, from October 2012 to January 2013.
The patients were randomly divided into 2 groups: Group A
(control) with compression therapy and group B with surgical treatment in addition to compressive therapy (experimental). Patients were evaluated weekly (8 weeks). At each
assessment, photographs and lesion measurements were
taken and pain was evaluated using the visual analog scale.
We indicated rest and elevation of lower extremities for 30
minutes in the morning and 30 minutes in the afternoon, as
Figure 1 Echographic image showing the veins that give terminal reflux to the venous ulcer.
56
O. F. López-Lugo et al
Figure 3 Image showing the avulsion of the vein with terminal
reflux to the venous ulcer with a hemostatic clamp.
Figure 2 Image showing the extraction with a hook of the vein
with terminal reflux to the venous ulcer.
well as sleeping with the affected limb elevated. Patients were discharged on an outpatient basis with analgesic (paracetamol 500 mg orally every 8 hours) in case of pain, and
treating the wound every 24 hours with a super-oxidized
antiseptic solution (Microdacyn®), non-adherent dressings
and mild compression elastic socks (20-30 mmHg).
In group B, using an ultrasound with lineal transducer of
7.5 MHz, with the patient standing, the researcher looked
for and marked the responsible vein(s) of the terminal blood
reflux to the ulcer (Fig. 1). Once we identified the vein(s),
we proceeded with: infiltration with local anesthesia (lidocaine 1%), a puncture with a Jelco® catheter #14 adjacent
to the marked vein, dermis dissection and vein extraction
with a hook (Fig. 2), avulsion of the vein with hemostat
clamps (Fig. 3), compression in order to achieve hemostasis,
application of a super-oxidized antiseptic solution (Microdacyn®), non-adherent dressings and mild compression elastic
socks (20-30 mmHg).
Statistical analysis
The information was gathered in a database using Excel®.
We performed the Kolmogorov-Smirnov test to evaluate the
variable distribution, and we determined that they all
showed a normal distribution (Gaussian). The other test
used to compare both groups was the Student’s T-test with a
95% confidence, and we considered it to be statistically significant p<0.05. We used the SPSS® Statistics version 20.0
(IBM Company). The study was approved by the Institution’s
Committee of Ethics.
Results
A total of 20 patients with active venous ulcers were included, 11 of them -9 female and 2 male- in group A (compressive therapy), and 9 of them -8 female and 1 male- in group
B (surgical and compressive therapy). No significant differences were found between the study groups in terms of
age, weight, height, BMI, ankle-brachial index, and baseline
measurement of the ulcer (Table 1). Venous ulcer mean diameter in week 1 was 4.04 cm (± 2.44) for group A and 4.75 cm
Table 1 Demographic data
Variable
Group A (n=11)
Group B (n=9)
p
Age, years,
average (± SD)
70.27 (± 16.3)
58.44 (± 14.2)
0.113
Weight, kg,
MEDIAN (± SD)
76.36 (± 12.57)
77.77 (± 6.74)
0.766
Height, m,
average (± SD)
1.62 (± 0.057)
1.62 (± 0.073)
0.900
BMI, kg/m2,
average (± SD)
28.98 (± 4.46)
29.44 (± 2.14)
0.780
ABI, mmHg,
average (± SD)
0.98 (± 0.087)
0.958 (± 0.06)
0.549
SD: standard deviation; BMI: body mass index; ABI: anklebrachial index.
(± 3.75) for group B with a p=0.616 (Table 2). Group B
showed a greater reduction in ulcer size and a statistically
significant lower score on the visual analog pain scale compared to group A (p<0.05) with full healing (scarring) in
3 patients. This difference was significant from the second
and third week of treatment, respectively (Table 3).
The average reduction in ulcer size during 8 weeks of follow-up for group A (compressive therapy) was 1.9 cm and
for group B (compressive therapy and surgical treatment)
was 3.4 cm with a confidence interval of 95% (Fig. 4).
Discussion
Based on this study, we were able to find that the medicalsurgical technique shown is better than the more conservative medical option. Favoring the results is the fact that no
significant differences were found between the study groups
in terms of age, weight, height, BMI, ankle-brachial index,
and baseline measurement of the ulcer. Although patients in
group B were younger (median age 58.44 years) than those
in group A (median age 70.27 years), age wasn’t significantly
distinct. All this makes the possibility of distractor variables
that could alter the final result less likely. Group B (medical
and surgical therapy) showed a statistically significant reduction in ulcer size and complete healing (scarring) in 3
57
Table 2 Measurement of the greatest diameter of the venous ulcer and the difference between 1-week and the week of the
evaluation.
Variable
Group A (n=11)
Group B (n=9)
p
Measurement 1-week, cm, average (± SD)
4.04 (± 2.44)
4.75 (± 3.75)
0.616
Measurement week 1-week 2
Difference in cm, average (± SD)
0.38 (± 0.25)
0.76 (± 0.53)
0.023
0.64 (± 0.45)
1.31(± 0.75)
0.025
1.054 (± 0.75)
1.4 (± 0.82)
0.028
1.29 (± 0.88)
2.3 (± 0.97)
0.026
1.56 (± 0.93)
2.64 (± 1.13)
0.025
1.7 (± 0.97)
2.97 (±1.32)
0.023
1.87 (± 1.02)
3.4 (± 1.71)
0.023
Group A (n=11)
Group B (n=9)
p
VAP week, 1, average (± SD)
7 (± 1.18)
7.66 (± 1.32)
0.250
5 (± 1.5)
4.77 (± 1.85)
0.774
4.36 (± 1.2)
2.55 (± 1.23)
0.004
3.81 (± 1.47)
1.33 (± 1.41)
0.001
3.0 (± 1.73)
0.77 (± 1.2)
0.004
2.9 (± 1.75)
0.55 (± 0.08)
0.002
2.36 (± 1.5)
0.33 (± 0.70)
0.002
2.27 (± 1.55)
0.33 (± 0.70)
0.003
SD: standard deviation.
Table 3 Values on the visual analog scale of the pain during follow-up weeks.
Variable
VAP: visual analog pain; SD: standard deviation.
5.00
Mean reduction
4.00
3.00
2.00
1.00
0.00
Group A
Group B
Study group
Error bars 95% confidence interval
Figure 4 Comparison of the reduction of the size of the ulcer
in centimeters between groups A (compression therapy) and B
(surgical and compressive therapy).
patients compared with group A. As Bush proves in his study
with ulcer treatment at 8 weeks (11 patients out of the 14
initially included), group B showed a lower score in the visual analog scale of pain compared with group A, which was
statistically significant from the third week of treatment.27
Considering the satisfactory evolution in group B with a
statistically significant decrease in pain and ulcer size, it
would be convenient to extend follow-up in order to evaluate complete healing in every patient within this group in
particular. In addition, it is important to determine venous
ulcer recurrence between both groups in order to demonstrate if there is a significant difference, as mentioned by
the Landmark study ESCHAR (Effect of Surgery and Compression on Healing and Recurrence in patients with venous
ulcers), which randomized 500 patients with advanced
chronic venous insufficiency. The first group included 258
patients treated with compression, a second group with
242 patients was treated with compression and surgery; a
58
Week 1 (4 cm)
O. F. López-Lugo et al
Week 4 (3.6 cm)
Week 8 (3 cm)
Week 1 (3 cm)
Week 3 (2.3 cm)
Week 8 (complete
healing)
Figure 5 Images of the follow-up of a patient from group A
(compressive therapy).
Figure 6 Images from the follow-up of a patient from group B
(surgical and compressive therapy).
recurrence after 12 months of 28% for the first group compared to 12% for the second group was found.28,29 The obtained results in this study of patients who underwent surgical
procedure (group B) concur with the efficacy reported by
Zamboni et al. in a randomized study of 45 patients with
venous ulcers, 24 patients with compressive therapy and 21
patients with postsurgical use of elastic socks, with healing
of 96% in a period of 63 days for the first group compared
with 100% healing in 31 days for the second group,30 with
the difference that in our study we utilized a minimally invasive procedure (microphlebectomy). Even though a sample of 20 patients is small (this being the study’s main
weakness), there is a clear tendency in favor of our experimental group. Another limitation of this study is a relatively
short follow-up period. Terminal interruption of reflux source technique guided by ultrasound proved with statistically
significant results to be more effective than the more conventional medical treatment to reduce pain and size of venous ulcers. The use of this surgical technique may be a
promising line of minimal invasion in venous ulcer treatment
in the immediate future. Further studies are required with
this surgical technique and a longer follow-up period in order to evaluate recurrences.
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the dependent legs of patients with venous hypertension: a
possible mechanism for trophic changes in the skin. Br Med J
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5. Hisley HR, Ksander GA, Gerhardt CO, et al. Extravasation of
macromolecules and possible trapping of transforming growth
factor beta in venous ulceration. Br J Dematol 1995;132:79-85.
6. Alexander CJ. The theoretical basis of varicose vein formation.
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the ulcer bearing skin of the leg. Br Med J 1982;2:243-245.
8. Browse NL, Burnand KG. The cause of venous ulceration. Lancet 1982;2:243-245.
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11. Kjaer ML, Mainz J, Soernsen LT, et al. Clinical quality indicators
of venous leg ulcers: development, feasibility, and reliability.
Ostomy Wound Manage 2005;51:64-74.
12. Bjellerup M. Does dorsal pedal pulse palpation predict handheld Doppler measurement of ankle-brachial index in leg ulcer
patients? Wounds 2003;15:237-240.
13. Lee YM, Ting AC, Cheng SW. Diagnosing deep vein thrombosis in
the lower extremity: correlation of clinical and duplex scan findings. Hong Kong Med J 2002;8:9-11.
14. Arseculeratne YM, Walton J, Hofman D, et al. A comparison of
light reflection rheography and duplex scanning in the diagnosis
of chronic venous insufficiency. Wounds 2003;15(8).
15. Carpentier PH, Cornu-Thenard A, Uhl JF, et al. Appraisal of the
information content of the C classes of CEAP clinical classification of chronic venous disorders: a multicenter evaluation of
872 patients. J Vasc Surg 2003;37:827-833.
16. Eklof B, Rutherford RB, Bergan JJ, et al. American Venous Forum International Ad Hoc Committee for Revision of the CEAP.
Revision of the CEAP classification for chronic venous disorders:
consensus statement. J Vasc Surg 2004;40:1248-1252.
17. Northeast ADR, Layer GT, Wilson NM, et al. Increased compression expedites venous ulcer healing. Royal Society of Medicine
Venous Forum, 1990.
18. Lorimer KR, Harrison MB, Graham ID, et al. Venous leg ulcer
care: how evidence-based is nursing practice? J Wound Ostomy
Continence Nurs 2003;30:132-142.
Funding
References
1. Callam MJ. Epidemiology of varicose veins. Br J Surg
1994;81:167-173.
2. Rabe E, Pannier-Fisher F, Bromen K, et al. Bonner Venenstudie
der Deutschen Gesellschaft fur Phlebologic epidemiologigische
Untersuchung zur Frage der Haufigkeit und Avspragung von
chronischen Venenkrakheiten inder stadtischen un landlichen
wohnbevolkerung. Phlebologic 2003;32:1-14.
19. Van Hecke A, Grypdonck M, Beele H, et al. How evidence-based
is venous leg ulcer care? A survey in community settings. J Adv
Nurs 2009;65:337-347.
20. Collins L, Seraj S. Diagnosis and treatment of venous ulcers. Am
Fam Physician 2010;81:989-996.
21. European Wound Management Association (EWMA). Position document: understanding compression therapy. London: MEP
Ltd.; 2003.
22. Gould DJ, Campbell S, Newton H, et al. Setopress vs Elastocrepe in chronic venous ulceration. Br J Nurs 1998;7:66-70.
23. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg
ulcers. Cochrane Database Syst Rev 2009;CD000265.
24. Ukat A, Konig M, Vanscheidt W, et al. Short-stretch versus multilayer compression for venous leg ulcers: a comparison of healing rates. J Wound Care 2003;12:139-143.
25. Myers KA, Ziegenbein RW, Zeng GH, et al. Duplex ultrasonography scanning for chronic venous disease: patterns of venous
reflux. J Vasc Surg 1995;21:605-612.
59
26. Adam DJ, Bello M, Hartshorne T, et al. Role of superficial venous surgery in patients with combined superficial and segmental deep venous reflux. Eur J Vasc Endovasc Surg 2003;25:469472.
27. Bush RG. New technique to heal venous ulcers: terminal interruption of the reflux source (TIRS). Perspectives in Vascular
Surgery and Endovascular Therapy 2010;22:194-199.
28. Barwell JR, Davies CE, Deacon J, et al. Comparison of surgery
and compression with compression alone in chronic venous ulceration (ESCHAR Study): randomized controlled trial. Lancet
2004;363:1854-1859.
29. Gohel MS, Barwell JR, Taylor M, et al. Long-term results of
compression therapy alone versus compression plus surgery in
chronic venous ulceration (ESCHAR): randomised controlled
trial. BMJ 2007;335:383.
30. Zamboni P, Cisno C, Marchetti F, et al. Minimally invasive surgical management of primary venous ulcers vs. compression
treatment: a randomized clinical trial. Eur J Vasc Endovasc
Surg 2003;25:313-318.
medicina
universitaria
www.elsevier.com.mx
Original article
Smoking, depression, and suicide risk in the nursing staff of a
Third-Level Hospital
R. A. Sánchez-Núñeza,*, C. Ramíreza, M. V. Gómez-Mezab
a
Department of Psychiatry, “Dr. José Eleuterio González” University Hospital, Monterrey, N. L., Mexico
b
Faculty of Economics, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: November 2013; Accepted: April 2014
KEYWORDS
Smoking; Depression;
Suicide risk; Mexico.
Abstract
Objective: To determine the association between smoking, depression and suicide risk in the
Nursing Staff of a University Hospital.
Materials and method: This was a non-experimental, correlational cross-range study with observational analysis carried out between May 2012 and May 2013. We studied 232 nurses of the “Dr.
José Eleuterio González” University Hospital.
Two self-administered scales were applied, one for depression and one for suicide risk. Another
hetero-applied scale of nicotine dependency was also used, and the subjects’ socio-demographic records were reviewed.
Results: A total of 527,232 nurses were studied. A smoking prevalence of 22.8% (53 subjects), an
operational depression prevalence of 15.1% (35 subjects), and a suicide risk of 5.1% (12 subjects) were found.
Gender and age, specifically being male and young (mean age 29.2 years) were found to increase the risk of smoking. We also found that those nurses who had a partner and had a higher level
of education smoked less compared to those who did not have a partner or had a lower degree of education. There were hospital departments where there was a higher prevalence of
smoking, such as Internal Medicine and Shock Trauma. No association between smoking and the
presence of depression was found.
Regarding depression, we found that those nurses who worked in the Department of Pensioners
were more likely to develop operational depression than those working in any other department.
We also found that the risk of presenting operational depression decreases as age increases.
About suicide risk, a statistically significant association between smoking and suicide risk was
found. We also found an association between operational depression and suicide risk.
* Corresponding author: Francisco I. Madero and Dr. Eduardo Aguirre Pequeño, Mitras Centro, Z.P. 64460, Monterrey, N. L. Mexico. Cell
phone: 52 (81) 8287 5681. E-mail address: [email protected] (R. A. Sánchez-Núñez).
Smoking, depression, and suicide risk in the nursing staff of a Third-Level Hospital
61
Conclusions: It is recommended to consider nicotine dependence as a fundamental part of
psychopathology assessment because of its strong association with suicide risk. This study
emphasizes the complexity of the issue of the comorbidity of smoking and psychopathology and
the need to continue research lines.
Introduction
Smoking is a risk factor for over 20 disease groups, and it’s
the number one cause of avoidable death.1 Tobacco addiction is one of the main causes of morbidity and impaired
quality of life. There is a strong connection between smoking and neurological and psychiatric disorders such as depression, schizophrenia, Parkinson’s and Alzheimer’s diseases.2 In
Mexico there is a higher prevalence of smoking among health
professionals (31.6%) in comparison with professionals in
other fields (23.5%). There are reports in which 29.3% of the
Nursing Staff was found to smoke.3
Depression is a syndrome characterized by a drop in mood,
self-esteem, ability to experience pleasure with emotional,
ideative, conductual and cognitive demonstrations; with serious repercussions on quality of life, social and work performance.4 It is the main cause of disability worldwide; it is
considered that by the year 2020 it will be the second cause
in absence from work in developed countries.2
The nursing profession is potentially stressing, amid health
professions it is considered to be amongst the top ones causing fatigue, trouble sleeping, substance abuse and psychiatric morbidities such as depression.5
Depression risk factors for health professionals are: Working with terminally-ill patients, interpersonal problems
with coworkers, clinical competition, fear of failure and excessive and demanding work.6 Working in areas with high
work demand, little autonomy and monotony have been associated with depression.7 The stress level in nursing is displayed with absences from work, depression, strong smoking
habits, or Burnout Syndrome.8 Other risk factors are extended work shifts, work overload, difficulty of working under
optimal time and equipment and personnel conditions, in
addition to rotating schedules and night shifts.5,9,10
Suicide is a public health problem. Depression is considered a common cause; around 75% of the people who commit
suicide suffer from depression. The majority of suicides are
not impulsive, those who attempt it do it after failed attempts at seeking help; therefore, there is not enough time
to help the victim.11
A strong link between smoking and depression has been
observed. We understand that people with a history of depression are more prone to smoke; depressive symptoms
that occur during abstinence are reversible with reinitiation
of smoking.2 However, there is little evidence that talks
about the mechanism influencing this link. There are 2 possible mechanisms:12 depression causes smoking because the
individuals with symptoms smoke as a self-medication to
reduce their depressive mood 2,12 or depression develops
from the neurochemical changes caused by smoking.
The common factor: both pathologies share genetic and
environmental factors which independently increase the
risk of both conditions.12
Women who smoke are twice as likely to present depressive symptoms, compared to those who do not smoke, and
five times more than men. Men who smoke more than a pack
a day, have a 500% higher possibility of presenting depressive symptoms compared to those who do not smoke. Those
who used to smoke or who currently smoke, have a higher
possibility of presenting depression compared to those who
have never smoked.13 The Nursing Staff of a hospital is a
specific population that simultaneously consumes tobacco
and has a risk of presenting depressive episodes and suffering the consequences from a depressive disease, interfering with their work, impairing their development and
performance, and with irreparable repercussions such as
suicide, therefore justifying the need for studies to have a
better understanding of its characteristics in order to develop integral strategies and treatments specifically for this
population. The purpose of this study is to determine the
connection between smoking, depression and risk of suicide
in the Nursing Staff of the “Dr. José Eleuterio González”
University Hospital.
Materials and method
This was a non-experimental, correlational cross-range study with observational analysis. We requested authorization
from the Hospital administration and Head of Nursing to obtain a list of the Nursing Staff, and with an error margin of
5% we calculated our sample in 232 nurses. We randomly
selected the subjects from the Nursing Staff in all of the
hospital’s areas and services. We invited them to voluntarily
participate and asked them to sign an informed consent
form. We applied 3 scales and a socio-demographic profile.
The scales we used were:
1. Zung Self-Rating Depression Scale: This scale was
used to determine the prevalence of depression in
the Nursing Staff. It may be applied and scored in a
few minutes, and is drafted in simple language, including 20 phrases using a 4-point Likert scale. One
of the statements in the scale is: “I feel down and
sad, I feel that people around me would be better
if I died”. In this study we denominated operative depression to the mood disorder detected in the Zung
Scale if the subject scored 36 or higher. The scale
has a sensitivity of 85% and specificity of 75% when
applied for case detection in a clinical population
or the general population.
2. Plutchik Suicide Risk Scale: Designed to evaluate
the risk of suicide, it is a self-rating tool. It consists
62
R. A. Sánchez-Núñez et al
of 15 items to which the subject may answer “yes”
or “no”. It includes questions about previous autolytic attempts, current suicidal ideation intensity
and feelings of depression and despair. Some of the
questions are: “Have you ever thought about ending your life?” Scoring is obtained by adding all
the points and may go from 0 to 15 points. Authors
propose a cutoff point of 6. It has been used to
determine risk of suicide in Nursing Staff.
3. Fagerström Test: It is a hetero-administered scale
which assesses nicotine dependency in people. It consists of 6 items with a series of answers associated
with a numeric value; values obtained in each one of
them are added. A subject is considered to have low
dependence with a score of 0-4, medium dependence
with a score of 5-6, and high dependence with a score
of 7-10. It was used to determine the correlation between nicotine and depressive symptomatology.
4. Socio-demographic profile: We asked about gender,
age, marital status, schooling, source of economic
support, current pregnancy, number of children,
area/department of work, and shift the Nursing
Staff was on.
Ethical Considerations
We contacted the members of the Nursing Staff who we detected to have severe depressive symptoms or a high risk of suicide; in order to secure their confidentiality, we contacted them
personally through the phone, and we informed them how to
make a free appointment in the Psychiatry Department.
The descriptive as well as the inferential statistical analysis was performed using SPSS® Statistics version 13. The categorical variables were obtained through absolute,
proportional and percentage frequencies, while continuous
numerical variables measurements of central tendency, variability and positioning were calculated. There were 2 types of estimates in this study, the point and the interval
estimates, with a 95% confidence interval In order to achieve the study objectives and prove the hypothesis, we obtained chi-square tests for contingency charts and adjusted
the logistic regression models.
Within the logistic regression model’s adjustment, we
considered as a complete model the one that included independent variables: shift (morning, afternoon, pilot, night),
gender (male and female), source of economic support (personal, partner and/or shared), smoker (yes and no), marital
status (with a partner, without a partner), Department
(pensioner and rest), down mood (short period of time and
another), and age in years. We implemented backward selection and obtained the best model to describe the behavior of the probability that Nursing Staff indicates operative
depression (Table 1). In a similar way, we worked to model
the probability of the presence of suicidal thoughts (Table
2).
Results
1. Sample characteristics
Of the 232 subjects, 193 (83.2%) were women and 39 (16.8%)
were men. Average age was 33.4 years (SD 12.4). Regarding
marital status, 127 (54.7%) subjects were single, 91 (39.2%)
Table 1 Adjustment of the final model of logistic regression for the probability of operative depression in Nursing Staff (n=228).
Variable
Age, years
B
-0.0473
Wald
6.44
gl
p
1
0.011
0.954
0.9196
0.9893
0.099
0.0310
0.3136
Department*
-2.3169
15.40
1
0.001
Constant
1.7961
4.19
1
0.041
Exp (B)
Inferior limit**
Superior limit**
* Department was analyzed considering 2 groups: 1) pensioners with a value of 0 and 2) the remaining pensioners or non-pensioners with
a value of 1. This second group included the Departments of Surgery, External Consultation, Leadership, Laparoscopy, Polyclinics,
Gynecology, Obstetrics and Labor and Delivery, Inhalotherapy, UCIA, Internal Medicine, Oncology, Pediatrics, Psychiatry, Operating
Room, X-rays, and Shock and Trauma. ** With a 95% confidence interval.
Table 2 Adjustment of the final model of logistic regression for the probability of suicidal thoughts in Nursing Staff (n=228).
Variable
B
Wald
gl
p
Exp (B)
Inferior limit**
Superior limit**
Age, years
-0.0432
4.38
1
0.036
0.9577
0.9198
0.9972
Depression*
-1.3878
10.19
1
0.001
0.2496
0.1065
0.5853
Constant
0.1627
0.06
1
0.808
* Depression is an artificial variable that was formed in accordance with the statement “I feel depressed and sad”, with a value of 0
when the response was “some of the time”, “a good part of the time” or “most of the time” and with a value of 1 when the response
was “almost never”. ** With a 95% confidence interval.
2. Prevalence
With a 95% confidence interval we found the following prevalences: for tobacco, 52 subjects (22.8%); operative
depression, 35 subjects (15.1%), and under suicide watch,
12 subjects (5.1%) (Table 3).
3. Characteristics of the group of nurses who smoke
(53 in total)
There were 37 females and 16 males, with a statistically
significant difference by gender. The males were more vulnerable to developing smoking habits (p=0.006). Average
age of male nurses who smoke was 29.2 years. We also
found that the younger the age the more likely they are to
smoke (p=0.015).
Regarding marital status, 37 subjects (71%) did not have a
partner and 16 (29%) did. About schooling, 27 had a technical degree (51.9%), 24 had a bachelor’s degree (46.2) and 1
had a master’s degree (1.9%). We found 2 protective factors
against smoking: having a partner (p=0.038) and having a
bachelor’s degree (p=0.048).
The areas/departments where subjects smoked the most
were Shock Trauma (10 subjects) and Internal Medicine (10
subjects); the areas/departments where subjects smoked
the least were Pediatrics (1 subject), Nursing Administration
(1 subject), and External Consultation (1 subject); there
were areas/departments where the subjects did not smoke
(Oncology and Neurology). Of the 53 nurses, 10 subjects had
suicidal thoughts and 6 subjects obtained a score of 6 or
greater on the Plutchik Suicide Risk Scale, which places
them as without risk of suicide.
4. Operative depression (36 to 80 points detected by
Zung Self-Rating Scale)
Table 3 Results. Frequencies (fr), percentages (%) and
limits of intervals of the 95% confidence interval.
Characteristic
fr
%
IL
SL
Active smoking (nicotine
dependency)*
Low
Moderate
Severe
53
48
2
2
22.8
21.1
0.9
0.9
Depressive symptoms**
Operative depression***
58
35
25.0
15.1
19.4
10.4
30.6
19.7
Suicidal thoughts****
Suicide risk*****
28
12
12.1
5.1
7.8
2.3
16.3
8.0
17.4
28.3
Of the 35 subjects with operative depression, 29 were females and 6 were males. Table 1 shows that the possibility
of nurses developing operative depression is greater in the
Department of Pensioners (Wald=15.40; p=0.001) compared
to the rest of the departments at the hospital; this probability decreases with the increasing age of the nursing professional (Wald=6.44; p=0.011) (Fig. 1).
Of the 35 subjects with operative depression, 8 smoked
and 27 did not. We found no statistically significant connection between smoking and displaying depressive or operative depression symptoms.
5. Suicide risk (greater or equal to 6 points detected
on the Plutchik Suicide Risk Scale, i.e., without risk
of suicide)
All of the 12 subjects found to have a suicide risk were females. Average age for suicide risk was 29.7 years. The variables which were significant to model the probability of
suicidal thoughts were age and “feeling down and sad’.
When the patient indicates he/she feels down and sad for a
“short time,” the probability of suicidal thoughts is lower
than when said health professional expresses feeling down
and sad “some of the time”, “a good part of the time” or
even “most of the time” (Wald=10.19; p=0.001). Additionally, Table 2 shows the probability of having suicidal thoughts
decreases when the nurse’s age increases (Wald=4.38;
p=0.036) (Fig. 2).
The probability of displaying suicide risk depends mainly on
2 factors. One is having operative depression (p=0.001). Eight
subjects out of the 12 with suicide risk, also displayed criteria
for operative depression and active smoking (p=0.05). Of the
12 subjects with suicide risk, 6 smoke. The ones who do
smoke have a probability of suicide risk of 0.113 and those
1.0
Operative depression probability
were married, 8 subjects (3.4%) were separated, and 6
(2.6%) were living together with someone. Economic support was shared in 56.5% of the cases (131 subjects), it
came exclusively from the subject of the study in 84 cases
(36.2%) and mainly from the partner in 17 cases (7.3%).
Departament
Non pensioners
Pensioners
0.8
0.6
0.4
0.2
0.0
10
IL: inferior limit CR 95%; SL: superior limit CR 95%.
* Fagerström test. ** Zung Depression Scale. *** Zung
Depression Scale equal to or greater than 36 points. ****
Plutchik Suicide Risk Scale. ***** Plutchik Suicide Risk Scale
equal to or greater than 6 points.
63
20
30
40
Age in years
50
60
70
Non-pensioner departments (Surgery, External Consultation,
Leadership, Laparoscopy, Polyclinics, Gynecology, Obstetrics
and Labor and Delivery, Inhalotherapy, UCIA, Internal Medicine,
Oncology, Pediatrics, Psychiatry, Operating Room, X-rays, and
Shock and Trauma).
Figure 1 Probability of presenting operative depression according to the department of the University Hospital where the
study was conducted.
64
R. A. Sánchez-Núñez et al
Probability of suicidal thoughts
0.5
I feel depressed and sad
Almost never
Sometimes, a good part of the time or most of the time
0.4
0.3
0.2
0.1
0.0
10
20
30
40
Age in years
50
60
70
“I feel depressed and sad” is a question asked in the Zung Depression Scale, which can be answered using a Likert scale of 1
to 4 points with the answers “almost never”, “sometimes”, “a
good part of the time”, and “most of the time”.
Figure 2 Probability of suicidal thoughts according to age.
who don’t have a probability of 0.033. Therefore, there is a
connection between smoking and suicide risk (p=0.05).
Discussion
When the causal factor has been studied, it has been demonstrated that depressive patients are more prone to
smoke than the general population and show an important
reduction in the severity of their symptoms with nicotine
consumption.2,13 Moreover, tobacco abstinence may trigger
depressive symptoms.12,13
Studies of patients undergoing anti-tobacco treatment
have revealed that when depressive symptoms appear during the sixth week and sixth month of abstinence, there is
a greater risk of relapsing. In the same way, it has been
proposed that people with depression smoke as a way of
self-medication against these depressive symptoms through
negative reinforcement.14 These patients have greater odds
of remaining in abstinence by receiving anti-depressive treatments like bupropion, fluoxetine, moclobemide or
nortriptyline. It was recently reported that the depressive
symptomatology level predicts the development of smoking
in non-smokers.2,12,13
The connection can also be studied conversely, in other
words, smoking as a cause of depression, since there is evidence that smokers and ex-smokers have an 80% higher probability of developing depression in comparison with those
who have never smoked.2 Comorbidity studies show that
depression is more frequently associated with intense smoking (more than 20 cigarettes a day) and nicotine dependence, more than with a “light” or “moderate” use of tobacco.12
When considering both possible comorbidity explanations
(common risk factors or causal association), there is evidence of a shared etiology between dysthymia and intense smoking. One of the possible causes of this shared vulnerability
is the fact that there is a genetic similitude shared amongt
relatives that gives specific character traits such as neurotic
traits and negative affectivity.12
Little is known about specific patient populations which
register smoking and depression simultaneously, and there
is a need for more information in order to implement integral treatments specific for this type of patient, taking into
consideration gender, depression severity and level of nicotine dependence. 13 This is the first assessment in Nuevo
León applied to a specific population and describing the
connection between depressive symptoms, socio-demographic characteristics and tobacco use. While some epidemiologic studies have demonstrated an independent association
between smoking and major depression, other studies have
shown that depression does not show a significant connection to smoking once comorbidity is adjusted.12
An indirect connection between smoking and depression
has been suggested. Depression has been associated with
tobacco consumption exclusively in the presence of comorbidity with behavioral problems. Other studies have found a
connection between smoking and light depressive symptoms, rather than smoking and major depressive disorders.13
Compared to non-smokers, heavy smokers are at a higher
risk of suicide. Suicide risk is related with the number of
cigarettes smoked daily. Smokers of 15 or more cigarettes
a day have a suicide risk 4 times higher than non-smokers.14
There are different characteristics among smokers and
non-smokers: the presence of depression, schizophrenia, alcohol and drug abuse, ideation and intention of suicide, a
greater risk of developing cancer, not being married and
being socially isolated. All of these risk factors are more
frequently displayed amongst smokers rather than nonsmokers. In addition, smokers have a higher tendency of acting hostile and having more anxiety.14
There are 4 possible explanations for the relationship between tobacco consumption and suicide:14
1. Depression is a common background to suicide, and
it is a condition that preconditions smoking as selfmedication.
2. Smoking produces chemical changes in the brain
which predispose to depression, which increases
the risk of suicide.
3. Smoking increases the risk of chronic diseases like
cancer, which predisposes to suicide.
4. Smoking is associated with other personal characteristics predisposing to suicide, such as low selfesteem, not because smoking lowers self-esteem,
but because in our culture they tend to occur simultaneously.
This study does not pretend to define the causality between smoking and psychopathology, given the complexity of
this matter and the multiple variables that should be studied; however, it does aspire to study some of the specific
situations in the Nursing Staff and the connection between
smoking and depression or suicide risk. We stress the need
to continue investigating this subject, since contrary to
what the literature shows, in this study we did not find a
connection between smoking and the presence of depressive symptoms. We could presume that the population within
the Nursing Staff is different from the rest of the population, and that as one of the hypotheses mentioned in the
previous text, smoking may be used as a self-medication
against depression, and that those nurses who smoke were
not detected with depressive symptoms for this reason.
There is evidence supporting that the Nursing Staff is under work stress and unfavorable working conditions, displaying psychopathology; this study detected the fact that
there is at least one hospital area/department which must
be studied more thoroughly in order to find specific stress
factors, because of its connection with operative depression
in its Nursing Staff. Just as reported in international literature, this study found an association between smoking and
suicide risk. Some of the study’s limitations are the fact
that we only considered Zung’s Self-Rating Scale to determine the presence or absence of depression (operative depression higher or equal to 36 points) and we did not perform a
structured interview which could define it in terms reflected in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) as a persistent depressive
disorder with mixed demonstrations. We did not consider
work stress factors such as double shifts or working life in
the study.
Conclusion
We recommend considering nicotine dependency a fundamental part in the evaluation of psychological aspects in
nursing professionals, because its association with suicide
risk was demonstrated. We highlight the importance of creating preventive measures for the Nursing Staff, like group
therapy to provide psycho-occupational support against
smoking, depression and suicide risk.
Funding
65
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medicina
universitaria
www.elsevier.com.mx
Original article
Effects of liraglutide on weight reduction and metabolic
parameters in obese patients with and without type 2 diabetes
mellitus
E. A. García-Cantúa,*, H. H. Alvarado-Saldañaa, H. E. Támez-Pérezb, G. Rubio-Aguilara
a
Cardiolink Clinical Trial, Monterrey, N. L., Mexico
b
Sub-direction of Research, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
KEYWORDS
Liraglutide; GLP-1;
Obesity; Overweight;
Type 2 diabetes
mellitus; Mexico.
Abstract
Objective: To evaluate the effect of liraglutide on body weight and metabolic parameters associated with cardiovascular risk in patient with or without type 2 diabetes mellitus (DM).
Methods: A descriptive, observational and analytical study was performed. A review was conducted on clinical records from patients seen in a cardiology private practice, who received
liraglutide as a weight -reducing adjunct, combined with prescription of several life style modifications as a 2000 kcal diet in men, or 1800 kcal diet in women and moderate daily aerobic
exercise ( at least 30 minutes, 5 times a week) during 3 months. Data from both, diabetic and
non diabetic obese patients with body mass index (BMI) >30 kg/m2 and at least two failed weight
lost attempts in previous twelve months were included. Thirty eight cases meeting these criteria were selected.
Results: An average of 4.8 kg of weight lost at the end of three months were observed (p<0.001).
Further benefits in several cardiovascular and/or metabolic risk factors such: as increased cHDL, decreased serum triglycerides and lowering of systolic blood pressure. Liraglutide showed
an adequate safety profile in these population, with only minor adverse reactions (nausea, dizziness, vomiting, diarrhea or constipation), which disappeared within the first two weeks of
treatment.
Conclusion: The effectiveness and security of liraglutide as an adjunct for weight loss were demonstrated. Liraglutide also showed beneficial effects improving metabolic risk factors leads to
cardiovascular disease
* Corresponding author: Cardiolink Educación. Hidalgo N° 1813 pte. St., Obispado, Monterrey, N. L., Mexico. Telephone: (81) 4040 1554.
E-mail address: [email protected] (E. A. García-Cantú).
Effects of liraglutide on weight reduction and metabolic parameters in obese patients
with and without type 2 diabetes mellitus
Introduction
Overweight and obesity are 2 major health problems in our
country, because of their prevalence, as well as the risk
they generate in the development of metabolic and cardiovascular diseases (these constitute the leading cause of
death in our country). According to the 2012 National Health
and Nutrition Survey, 26 million adult Mexicans were overweight and 22 million were obese.1 Because of the multiple
variables that play a role in the genesis of obesity, this condition creates a challenge for health professionals that can be
difficult to overcome. Different drugs have been used as
coadjutants in the handling of this disease; however, their
use has been limited, and in some cases suspended due to
the adverse reactions generated, which in some cases has
been fatal.2
Glucagon-like peptide-1 (GLP-1) analogues are drugs developed for type 2 diabetes mellitus (DM) management.3,4
Liraglutide is the second medication approved by the Food
and Drug Administration (FDA).5 One of its advantages is leading to less hypoglycemia events compared with other oral
antidiabetics.6-8 In addition to lower glucose levels, we are
able to observe a decrease in body weight9 and an improvement in insulin secretion in patients who receive this medication.10 Other studies have reported the decrease in cardiovascular risk factors. 11 The mechanism of action of
GLP-1’s incretin is well defined. It is produced in ileocolic C
cells stimulating pancreatic secretion of insulin by interaction with a G protein.12,13 At a gastrointestinal level, liraglutide decreases acid gastric secretion and delayed gastric
emptying by antral stimulation. Moreover, it inhibits propulsion of pylorus, and decreases motility in the digestive tract
after food intake. It also induces early satiety through the
central nervous system through a mechanism which is not
yet specified, yet it is thought to be AMPc stimulation.12,13
Furthermore, the possibility of the activation of neuronal
receptors at the satiety center in the hypotalamus at the
arcuate nucleus, has been suggested, as well as the inhibition of the solitary tract of the brain stem. Altogether, the
diverse mechanisms mentioned favor a reduction in the caloric intake, which could result in weight loss.12,13
The objective of this study is to evaluate the effect of liraglutide on body weight and metabolic parameters associated
with cardiovascular risk, in patients with or without type 2 DM.
We conducted a descriptive, observational, analytical study,
in which clinical files of patients cared for from July 2011 to
June 2012, in private cardiology practices in Monterrey, N.
L., Mexico were reviewed. We selected those who were
being prescribed liraglutide (from 0.6 to 1.8 mg every 24
hours) in addition to being told to follow a diet of 2000 kcal
for men and 1800 kcal for women, as well as the indication
to perform moderate exercise for 30 minutes at least 5 times a week. We selected those who met the following criteria: having received liraglutide treatment for at least a
period of 3 months, having registered the following variables at the beginning of the study and following 3 months of
treatment: Body weight, body mass index (BMI, calculated
using the following formula: weight in kilograms/square of
67
body length in meters), blood pressure measured with an
aneroid monitor, plasma glucose after fasting, lipid profile,
glycosylated hemoglobin and hepatic function tests measured with the basic and routine laboratory techniques, body
fat percentage obtained through impedanciometry using a
Tanita® Innerscan, mention of presence or absence of cardiovascular or digestive symptoms, and medication dosage
prescribed.
Administered liraglutide dosage was 0.6 mg a day during
the first week, which was gradually increased to 1.2 mg and
up to 1.8 mg a day according to tolerability and requirement. In addition, we prescribed metformin to 14 out of 15
diabetic patients and 13 out of the 23 non-diabetic patients.
For statistical analysis we utilized measures of central
tendency and dispersion. In order to compare quantitative
variables we used the Student’s T-test for both groups and
analysis of variance when we analyzed more than 2. We
used the statistical software SPSS® Statistics version 19.0.
We consider a p < 0.05 as significant.
Results
We included 38 cases which met the criteria. There were 23
(60%) males and 15 (40%) females, with an average age of 56
± 10 years. Fifteen patients (40%) were under type 2 DM
treatment. Other demographic variables are listed in Table 1.
Average weight loss at the end of 3 months of treatment
was 4.8 kg in 38 patients (p < 0.001), which was significant.
These results, as well as the rest of the evaluated parameters are shown in Table 2.
We observed a significant weight loss in diabetic patients
(4.2 kg) as well as in non-diabetic ones (5.2 kg). Furthermore, we observed an improvement in several evaluated metabolic parameters (Tables 3 and 4). The analysis of variance
displayed a non-significant difference in the behavior between subgroups in weight reduction, BMI, body far percentage, serum triglycerides, total cholesterol and c-LDL;
differences found in systolic arterial pressure and c-LDL
were significant.
Six patients (16%) reported an adverse event of moderate
intensity and relative frequency during the first 2 weeks of
treatment, particularly nausea, dizziness, vomiting, diarrhea and constipation; headaches and cramps occurred less frequently. There were no reports of hypoglycemia episodes or
hepatic enzyme alterations (TGO, TGP). Patients with heart
diseases did not display data of cardiac decompensation.
Table 1 Comorbidities present in study participants.
N
%
Smoking
7
18
Arterial hypertension
26
68
Dyslipidemia
21
55
Genetic tendency toward coronary heart
disease
26
63
68
E. A. García-Cantú et al
Table 2 Average (Avg), standard deviation (SD) and difference in the evaluated parameters in all patients, before and after
the administration of the drug (n=38).
Before
Weight (kg)
After
Avg
SD
Avg
SD
Difference
p
98.7
6.0
93.8
5.7
- 4.8
< 0.001
Body fat (%)
35.6
2.4
33.1
6.4
- 2.5
< 0.001
Body mass index (BMI)
33.0
2.0
31.4
31.8
- 1.6
< 0.001
Systolic blood pressure (mmHg)
137.7
7.5
132.2
0.4
- 5.6
< 0.001
Glucose (mg/dl)
124.1
41.4
117.1
20.0
- 6.9
NS
HbA1c*
Total cholesterol (mg/dl)
8.4
0.6
7.9
3.2
- 0.5
NS
211.5
14.4
208.7
9.3
- 2.8
NS
c-HDL (mg/dl)
35.4
2.7
38.3
17.9
2.9
< 0.001
c-LDL (mg/dl)
128.7
12.1
127.8
2.5
- 0.9
NS
Triglycerides (mg/dl)
178.5
19.7
169.1
1.9
- 9.4
< 0.001
* Glycosylated hemoglobin was only measured in diabetic patients.
NS: non-significant.
Table 3 Average (Avg), standard deviation (SD) and difference between the evaluated parameters in patients with type
2diabetes mellitus, before and after the administration of the drug (n=15).
Before
Weight (kg)
After
Avg
SD
Avg
SD
Difference
p
96.8
7.0
92.6
6.6
- 4.2
< 0.025
Body fat (%)
34.9
2.7
33.6
2.7
- 1.4
< 0.001
32.4
2.4
30.9
2.2
- 1.4
NS
134.4
7.6
131.6
6.5
- 2.8
NS
Glucose (mg/dl)
172.7
17.4
154.1
15.1
- 18.6
NS
HbA1c
8.4
0.6
7.9
0.4
- 0.5
NS
221.3
11.9
228.7
11.9
7.4
NS
c-HDL (mg/dl)
35.3
2.3
37.6
2.2
2.3
< 0.001
c-LDL (mg/dl)
117.7
9.1
126.3
10.7
8.5
< 0.025
188.9
17.4
175.3
18.9
- 13.7
NS
Discussion
Different studies and trials in which liraglutide has been administered, have proven the usefulness of this medication in
weight loss in obese patients with type 2 DM, as well as
in patients without this condition. Weight losses between 7 to 9
kg in 20 weeks have been reported, obtaining best results when
using 3 mg of liraglutide a day.14-18 It has been proven superior
when compared to placebo (2.8 kg) and orlistat (4.4 kg).11
In this study, the obtained weight loss was slightly lower than that reported, which can be attributed to a smaller dose and a shorter duration of treatment.
An important parameter to evaluate weight loss is body
fat percentage, because body fat at the abdominal level
constitutes a risk factor for the development of metabolic
syndrome. A publication reports a 1.2-1.9% decrease in body
fat.18 In the present study we observed that at the end of 3
months of treatment, body fat had lowered 2.5% on average, which was slightly greater than that reported.
An improvement of different metabolic parameters when
using liraglutide by itself, or in combination with other glucose-lowering drugs has been reported. Previous studies
show reductions of up to 1.7% on glycosylated hemoglobin,
a decrease in triglycerides of 22 mg/dl, and in fasting plasma glucose of up to 43.2 mg/dl.11,14,15
In this study, we are able to see that glycosylated hemoglobin and triglycerides values decreased even if it was to a
smaller degree than that reported.
Effects of liraglutide on weight reduction and metabolic parameters in obese patients
with and without type 2 diabetes mellitus
69
Table 4 Average (Avg), standard deviation (SD) and difference between the evaluated parameters in patients without type
2diabetes mellitus, before and after the administration of the drug (n=23).
Before
Weight (kg)
After
Avg
SD
Avg
SD
Difference
p
99.9
5.0
94.7
5.1
- 5.2
< 0.001
Body fat (%)
36.0
2.0
32.8
2.4
- 3.2
< 0.001
33.3
1.7
31.7
1.7
- 1.7
0.001
139.9
6.6
132.6
6.4
- 7.3
< 0.001
Glucose (mg/dl)
92.3
4.7
93.0
3.6
0.7
NS
205.1
12.3
195.6
11.6
- 9.5
< 0.05
c-HDL (mg/dl)
35.4
3.0
38.7
3.6
3.3
< 0.001
c-LDL (mg/dl)
135.9
7.6
128.8
8.3
- 7.1
< 0.01
171.7
18.3
165.0
16.3
- 6.7
< 0.001
A study had shown the reduction of systolic blood pressure
of 6.1 mmHg on average.11
In our study the reductions in blood pressure were slightly
superior to those reported in the literature.
Diverse side effects have been reported. Over 10% of the
patients have presented gastrointestinal discomfort (nausea, vomiting and diarrhea); consequently, dose should be
titrated in order to avoid the main adverse gastrointestinal
effects.19 From 1% to 10% of patients developed upper tract
respiratory infections, headaches and high levels of anti-liraglutide antibodies.19,20 It has not been possible to demonstrate the relationship between liraglutide and pancreatitis,
thyroid C-cell hyperplasia, and thyroid papillary carcinoma.21,22
In our study, 16% of the patients showed minor adverse
gastrointestinal reactions (i.e. nausea and diarrhea), which
disappeared within the first two weeks of treatment. There
were no hypoglycemia or pancreatitis cases, which could be
related to the selection of patients or the sample size.
The study has several limitations: is a retrospective, descriptive, and non-randomized design, with a small sample
size, as well as a short timeframe.
Conclusions
The effectiveness of liraglutide as an adjunct for weight loss
was demonstrated in patients with a BMI greater than 30 kg/
m2, with or without type 2 DM, with at least 2 failed attempts at losing weight in the last 12 months, successfully
losing an average weight of 4.8 kg in 3 months of treatment.
In the case of type 2 DM patients, we obtained an improvement in glycosylated hemoglobin, fasting glucose, blood
pressure and triglycerides, which theoretically shows a beneficial effect improving metabolic risk factors that lead to
cardiovascular disease. The drug’s safety profile was adequate, with minimal adverse effects.
It is important to note that the present study was not a
controlled clinical study, because of which the obtained results are based on real life private office patients.
Funding
References
1. Accessed on March 2014. http://www.insp.mx/images/stories/
Produccion/pdf/131011_ENSANUT2012.pdf
2. Pinto ME, Manrique HA. Retiro de sibutramina por riesgo de enfermedad cardiovascular. Rev Peru Med Exp Salud Publica
2010;27:489-490.
3. Croom KF, McCormack PL. Liraglutide: a review of its use in
type 2 diabetes mellitus. Drugs 2009;69:1985-2004.
4. Sakauye SD, Shah SA. Focus on liraglutide: A human GLP-1 analogue for the treatment of type 2 diabetes. Formulary
2009;44:136-142.
5. Amylin D. Alkermes shares benefit from FDA OK of Novo’s Victoza. BioWorld 2010;21:1-3.
6. Blonde L, Russell-Jones D. The safety and efficacy of liraglutide
with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab
2009;11(Suppl 3):26-34.
7. Sullivan SD, Alfonso-Cristancho R, Conner C, et al. Long-term
outcomes in patients with type 2 diabetes receiving glimepiride
combined with liraglutide or rosiglitazone. Cardiovasc Diabetol
2009;26:8-12.
8. Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide vs insulin
glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met +
SU): a randomised controlled trial. Diabetologia 2009;52:20462055.
9. Feinglos M, Saad M, Pi-Sunyer F, et al. Effects of liraglutide
(NN2211), a long-acting GLP-1 analogue, on glycaemic control
and bodyweight in subjects with type 2 diabetes. Diabet Med
2005;22:1016-1023.
10. Vilsboll T, Brock B, Perrild H, et al. Liraglutide, a once-daily
human GLP-1 analogue, improves pancreatic B-cell function
70
and arginine-stimulated insulin secretion during hyperglycaemia in patients with type 2 diabetes mellitus. Diabet Med
2008;25:152-156.
11. Courreges JP, Vilsbøll T, Zdravkovic M, et al. Beneficial effects
of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with type 2
diabetes. Diabet Med 2008;25:1129-1131.
12. Silva AM, Lopes CM, Misler S, et al. Glucagon-like peptide 1:
biochemistry, secretion and main physiological effects. Revista
de Faculdade Ciencias da Saúde 2009;6:104-113.
13. Neumiller JJ. Differential chemistry (structure), mechanism of
action, and pharmacology of GLP-1 receptor agonists and DPP-4
inhibitors. J Am Pharm Assoc 2009;49 (Suppl 1):S16-S29.
14. Joffe D. Liraglutide: a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes mellitus. Am J Health Syst
Pharm 2010;67:1326-1336.
15. Marre M, Shaw J, Brändle M, et al. Liraglutide, a once-daily
human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight
control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med
2009;26:268-278.
E. A. García-Cantú et al
16. Gallwitz B, Vaag A, Falahati A, et al. Adding liraglutide to oral
antidiabetic drug therapy: onset of treatment effects over
time. Int J Clin Pract 2010;64:267-276.
17. Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in
the treatment of obesity: a randomised, double-blind, placebocontrolled study. Lancet 2009;374:1606-1616.
18. Jendle J, Nauck MA, Matthews DR, et al. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue
for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab 2009;11:1163-1172.
19. Peterson GE, Pollom RD. Liraglutide in clinical practice: dosing,
safety and efficacy. Int J Clin Pract Suppl 2010;167:35-43.
20. Raskin P, Mora PF. Glycaemic control with liraglutide: the phase
3 trial programme. Int J Clin Pract Suppl 2010;167:21-27.
21. Rosebraugh Curtis PM. Weighing risks and benefits of liraglutide
- The FDA’s review of a new antidiabetic therapy. N Engl J Med
2010;362:774-777.
22. Moses A. Novo Nordisk replies to BMJ investigation on incretins
and pancreatic damage. BMJ 2013;347:386.
medicina
universitaria
www.elsevier.com.mx
Scientific letter
Dyke-Davidoff-Masson syndrome: A case study
M. A. Duncan*, S. Vázquez-Flores, E. B. Chávez-Lluévanos, A. C. Cantú-Salinas, L. de
León-Flores, H. J. Villarreal-Velázquez
Service of Pediatric Neurology, Department of Neurology, “Dr. José Eleuterio González” University Hospital, Faculty of
Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: July 2013; Accepted: January 2014
KEYWORDS
Dyke-Davidoff-Masson
syndrome; Cerebral
hemiatrophy; Facial
asymmetry; Mexico.
Abstract Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a rare condition first
described in 1933, with characteristic clinical and radiological features such as facial asymmetry,
hemiplegia, seizures, mental retardation, cerebral hemiatrophy, and skull and frontal sinus
abnormalities. We describe the clinical features, brain imaging and clinical course of a 13 yearold patient with this syndrome.
Introduction
Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome
(DDMS) is a rare condition, which may be congenital or develop in early childhood. In 1933, Dyke, Davidoff and Masson
first described the syndrome in a series of 9 patients with
hemiplegia and cranial asymmetry in plain cranial X-rays.
However, since then there have been few pediatric cases
reported.1-3 The syndrome is characterized by facial asymmetry, seizures, hemiplegia or contralateral hemiparesis,
and mental retardation of variable severity.1,3,4 It occurs in
both genders, with a predominance in males (73.5%). 5 A
diagnosis is usually made during late childhood, adolescence or adulthood.6 The etiology can be congenital or acquired
as a result of an alteration in the cerebral perfusion during
prenatal, perinatal or early childhood periods.1,4,5,7,8 The brain scan (CT) or magnetic resonance imaging (MRI) is utilized
to perform a diagnosis and specific findings include unilateral
brain volume loss and compensatory bone alteration resulting
in cerebral hemiatrophy, usually on the left hemisphere
(69%). In addition, ipsilateral cranial hypertrophy, overdevelopment of the orbital roof and hyperpneumatisation of
frontal sinuses may occur.4,5,7,9,10
Case presentation
A 13-year-old female, product of a fourth pregnancy, with a
history of a monozygotic twin pregnancy, full term with
* Corresponding author: Service of Pediatric Neurology, Department of Neurology, “Dr. José Eleuterio González” University Hospital, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico. Telephone: (044) 818 016 9944. E-mail address:
[email protected] (M. A. Duncan).
72
M. A. Duncan et al
adequate weight and no contingencies, normal psychomotor
development up to the first year of age, when a gait alteration with right hemibody weakness was noticed. She was
admitted to the Pediatric Neurology Service at “Dr. José
Eleuterio González” University Hospital after presenting
simple partial seizure with motor symptoms at age 7. An
electroencephalogram (EEG) was performed with normal results, and the patient was controlled with 400 mg/day of
oral carbamazepine. During the physical exam the patient
displayed hemifacial atrophy of the right side causing asymmetry (Fig. 1), right spastic hemiparesis with atrophy, hyperreflexia, ipsilateral extensor plantar response and a
hemiplegic gait. We are able to observe in the brain MRI
a reduction of ridges and grooves in the left frontoparietal
region, associated with ectasia of the ipsilateral ventricle,
which is compatible with cerebral hemiatrophy of the left
frontoparietal lobe (Figs. 2 and 3). The patient is currently
stable with proper control of seizure crisis and an adequate
level of antiepileptic medication (9.0 µg/dl). She is attending our integral follow-up service and rehabilitation.
Discussion
Cerebral hemiatrophy or DDMS is an entity characterized by
seizures, hemiplegia or hemiparesis and mental retardation.1,4,5,9 The condition may be congenital or acquired. In
the congenital form, there are usually no evident etiological
factors and symptoms present at birth or shortly after. Cerebral damage is likely due to an intrauterine vascular occlusion during the prenatal period. In the acquired form, symptoms are related to a damage of the central nervous
system occurring around or after the perinatal period. Some
of the etiological factors include trauma, infection, vascular
Figure 1 A 13-year-old female in whom facial asymmetry is
observed.
Figure 2 Axial magnetic resonance imaging (MRI), T2 FLAIR
sequence which shows left frontoparietal atrophy with ipsilateral ventriculomegaly.
anomalies, hemorrhagic and ischemic conditions, amniotic
bands, and an intraventricular and subependymal germinal
matrix.5,8,10 The mechanism of cerebral atrophy remains
unknown.1 Our patient displayed symptoms during an early
stage of her development; moreover, because of the history of being a product of a twin pregnancy, a high risk state
during pregnancy and the lack of evidence of injury during
postpartum, most likely the damage occurred during the
prenatal stage. Seizures do not always appear during early
childhood and often begin months or years after the hemiparesis onset.3,4 Sometimes patients display refractory
epilepsy, and the treatment must focus on seizure control
with anticolvulsant medication being either mono or polytherapy.5 Children with refractory epilepsy and hemiplegia
are potential candidates for hemispherectomy, with a success rate of 85%. Vagal stimulation is another alternative.
There is evidence that 30%-50% of patients with partial epilepsy may experience a decrease in convulsions in over 50%
of the cases.3 The prognosis is better if the hemiparesis appears after the first 2 years of age and in absence of recurrent and prolonged epilepsy. This syndrome is a rare
condition, with few cases described in medical literature and limited experience in pediatric patients. It is important to keep it in mind when dealing with a patient with
facial asymmetry associated with neurologic hemiplegia
data, seizures, and mental retardation, in order to perform
a correct diagnosis and proper care. Even though an established protocol for management is lacking, there is the indication for therapy including anticonvulsants and surgery in
specific cases. In addition, physical therapy, occupational
therapy and language therapy play significant roles in the
long term management of the patients.5
Dyke-Davidoff-Masson syndrome: A case study
73
Funding
References
Figure 3 Coronal magnetic resonance imaging (MRI), T2 FLAIR
sequence which shows interhemispheric asymmetry with atrophy and left ventricular ectasia.
1. Paudel K, Venugopal A. Dyke-Davidoff-Masson Syndrome. JNMA
J Nepal Med Assoc 2013;52:272-274.
2. Sharma S, Goyal D, Negi A, et al. Dyke-Davidoff Masson Syndrome. Ind J Radiol Imag 2006;16:165-166.
3. Erdem A, Acik V, Leventoğlu A, et al. Effect of vagal nerve stimulation in Dyke-Davidoff-Masson syndrome with refractory generalized seizures - case report. Turk Neurosurg 2009;19:197-199.
4. Aguiar PH, Liu CW, Leitão H, et al. MR and CT imaging in the
Dyke-Davidoff-Masson syndrome. Report of three cases and
contribution to pathogenesis and differential diagnosis. Arq
Neuropsiquiatr 1998;56:803-807.
5. Behera MR, Patnaik S, Mohanty AK. Dyke-Davidoff-Masson syndrome. J Neurosci Rural Pract 2012;3:411-413.
6. Piro E, Piccione M, Marrone G, et al. Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery. Ital J Pediat. 2013;14:39-32.
7. Zúñiga-González EA, Molina-Carrión LE, Diego-Silva RC. Síndrome de Dyke-Davidoff-Masson y hemiatrofia cerebral del adulto.
Informe de casos. Rev Med Inst Mex Seguro Soc 2009;47:215-218.
8. Lee JH, Lee ZI, Kim HK, et al. A case of Dyke-Davidoff-Masson
syndrome in Korea. Korean J Pediatr 2006;49:208-211.
9. Narain NP, Kumar R, Narain B. Dyke Davidoff- Syndrome. Indian
Pediatr 2008;45:927-928.
10. Shrestha B. Acquired cerebral hemiatrophy: Dyke-DavidoffMasson Syndrome – A case report. Turk Neurosurg 2013;23:117121.
medicina
universitaria
www.elsevier.com.mx
Scientific letter
Caudal regression syndrome: A case report
M. A. Duncan*, A. C. Cantú-Salinas, D. L. Villarreal-Rodríguez, C. Muñiz-Landeros, H. J.
Villarreal-Velázquez
Service of Pediatric Neurology, Department of Neurology, “Dr. José Eleuterio González” University Hospital, Faculty of
Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: September 2013; Accepted: January 2014
KEYWORDS
Caudal regression
syndrome; Caudal
dysplasia sequence;
Sacral regression
syndrome; Sacral
agenesis; Mexico.
Abstract Caudal regression syndrome (CRS) is a congenital malformation with a low incidence
in the general population. The true pathogenesis is unknown although there is a clear relation
with maternal diabetes. Prenatal diagnosis and imaging studies allow for reliable recognition and diagnosis. The physical exam and the diagnostic test necessary in the newborn period
allow for the identification of likely complications and establishing a prognosis. We present a
clinical case of a female neonate with a prenatal diagnosis of CRS, describing the workup and
management of this patient.
Introduction
Caudal regression syndrome (CRS) is an infrequent disorder
first described by Geoffroy Saint-Hilaire and Hohl in 1852, and
in 1964 Duhmel coined the term “caudal regression syndrome”.1-3 The CRS is a disorder caused by an anomaly of the
distal spinal segments, and it extends to a wide range of anomalies like partial agenesis of the spinal cord, associated pelvic malformations, imperforate anus, genital malformations,
cardiac anomalies, bilateral renal dysplasia or aplasia, pulmonary hypoplasia, and extreme external rotation with inferior
joints fusion resulting in the most grave form in sirenomelia
(mermaid syndrome). The CRS is also associated with femoral
hypoplasia, deformed feet and lower extremity flexion contracture. Intelligence is preserved, in general.1,2,4 It affects
between 0.1 and 0.25 out of every 10,000 pregnancies, with a
male-female ratio of 2.7:1.3-5 At an embryonic level, it is believed that CRS is the result of defects in the induction of
caudal elements in the embryo prior to the 28th day of gestation. The injury is produced in the posterior medial mesodermic axis causing the absence of development of the caudal mesoblastic yolk.4,6 The exact etiology is unknown; however, maternal diabetes, genetic predisposition and vascular
hypoperfusion have been suggested as possible factors.4-7
* Corresponding author: Service of Pediatric Neurology, Department of Neurology, “Dr. José Eleuterio González” University Hospital, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico. Telephone: (044) 818 016 9944. E-mail address: [email protected] (M. A. Duncan).
Pre-gestational diabetes is without a doubt a teratogen,
and there is good evidence that gestational diabetes may be
implicated in the development of the most severe form of
CRS.5
Pinter and Reece proved that alterations induced by hyperglycemia in the closing of the neural tube include disordered cells, decrease of mitosis, and changes which indicate
a premature maturation. The oxidative metabolism altered
by maternal diabetes can cause an increase in the production of oxygen-free radicals in the developing embryo,
which can be teratogenic.8 Between 16% and 22% of CRS cases are associated with maternal diabetes mellitus, which
increases the risk of having a child with CRS by up to 400.3,4,7
Several cases of families with CRS have been reported,
which suggests a possible genetic transmission with different possible transmission modes: X-linked dominant, multifactorial polygenic, and autosomal dominant patterns with
reduced penetrance and variable expressivity.7 The “vascular theft” theory was initially proposed by Kampmeier in
1927 and re-introduced in 1986 by Stevenson. Adra et al.,
considered Stevenson’s “vascular theft” theory as a possible
etiology of the CRS pathology.7 During the embryonic development stage the more caudal structures are separated
from the cephalic elements such as the brain, the spine,
and the spinal cord, hence the lack of cognitive alterations
in this syndrome.4
There are 2 CRS groups: the first group is the most affected with the termination of the spinal cord above L1. The
sacrum ends at S1, and in some cases, is absent. Patients in
the second group display a less severe dysgenesis with a low
implantation of the spinal cord and tethered by a thickened
filum terminale or intraspinal lipoma.4
Case presentation
We present the case of a newborn girl from a 40-year-old
mother with a medical history of untreated uterine fibroids,
a background of irregular gynecology cycles, 3 pregnancies
with 2 deliveries and cholecystectomy in 2008. She mentions an unplanned yet wanted pregnancy, with a high-risk
pregnancy prenatal care. She attended over 15 prenatal
consults. At the 18th week of gestation, compatible data
with malformations of the neural tube with sacral agenesis
was found, resulting in a CRS diagnosis. During the second
trimester of pregnancy hyperglycemia was detected, therefore she was placed on insulin treatment. At 40 weeks of
gestation, C-section was performed obtaining a healthy product, with an Apgar score of 8/9 with a gestational age
of 39.6 weeks. At the physical exam we observed a weight of
3.44 kg (7.58 lbs), a length of 49 cm (19.2 in), a head circumference of 35 cm (13.77 in) and an abdominal circumference of 32 cm (12.59 in). During inspection we were able to
observe an evident diabetic fetopathy, with abundant hair,
and low implantation (Fig. 1). Normal anterior fontanelle (2
x 2 cm), round face, prominent cheekbones, horizontal palpebral fissures, short nasal bridge, round tip, thin lips, full
palate, dysplasia of the auricular pavilions with hypertrichosis of the helix, short neck with a dorsal bulge, normal
thorax, without murmurs during auscultation, the abdomen
was soft without palpable masses or visceromegaly, linear
spine with presence of a dimple on the skin at lumbosacral
75
Figure 1 Newborn with diabetic fetopathy.
region (Fig. 2), no sacrum bone was palpable, normal position of the anus, permeable, with an absent tone. There
was an evident shortening of the lower extremities and bilateral varus club foot (Fig. 3). X-rays were taken in order to
see the bone malformations, and we were able to observe
complete agenesis of the sacrum with a lumbar-iliac fusion.
A brain and spine magnetic resonance imaging (MRI) (Fig. 4),
reported an abrupt chord and lumbar termination at L3 level. After this level we are able to identify only amorphous
masses with fat signal intensity, related to subcutaneous tissue. Short spinal cord, flat conus medullaris at T10 level,
both iliac bones were hypoplastic, and fused at mid-level.
We are not able to see the sacrum. It was possible to see
both kidneys malrotated and hypoplastic, a prominent urinary bladder compatible with a neurogenic bladder. The
brain image was reported as normal. An upper abdomen
echography was requested in order to rule out other visceral
anomalies finding a discrete discrepancy in the size of the
left kidney, in addition to not finding its normal configuration, which suggested discrete hypoplasia as well as a possible
malrotation. During their stay we performed multidisciplinary
consultation, and cast splints were placed on both lower
limbs. The patient remains in follow-up with Urology, Traumatology, Neurology and General Pediatrics, this in order to
keep a close watch on all the risk factors and possible complications.
76
Figure 2 A dimple on the skin at the lumbosacral region.
M. A. Duncan et al
Figure 3 Equinovarus feet.
Discussion
The CRS is a rare congenital malformation. Even though the
specific etiologic factor is unknown, it is related to maternal
diabetes, genetic predisposition and vascular hypoperfusion.3 Just as in the case presented, this alteration is characterized by agenesis of the sacrum involving iliac and lumbar
vertebrae with their corresponding spinal segments and variable abnormalities in the lower limbs as well as in other
organs. Fetal diagnosis tools allow early syndrome detection. Prenatal ultrasound is the most frequently used paraclinical instrument; a key element of prenatal ultrasound is
the detailed evaluation of the spine and lower limbs; it also
allows for a CRS diagnosis through the demonstration of an
abrupt termination of the lumbar spine and hypoplastic
lower limbs. When making a prenatal diagnosis, we must
focus on discerning the degree of digenesis as well as the
associated congenital anomalies with the purpose of establishing a prognosis and a timely plan of postnatal therapeutic interventions. 3,5 Renshav’s classification, which was
created in 1978, categorizes the syndrome in 4 degrees based on the severity of agenesis of the sacrum, and involvement of iliac and lumbar vertebrae. 9 According to this
classification, our patient belongs to grade IV (complete
agenesis of the sacrum with iliac-bones fusion). This group
is associated with an even worse prognosis with a greater
neurological impact and multisystemic sequels, mainly at a
renal level. This case is a clear example of the wide range of
alterations that can affect the growing fetus as a result
of uncontrolled maternal diabetes during pregnancy. Because of the high correlation between this defect and the diabetic mother, and its development during the early stages of
pregnancy, it is imperative to have a preventative strategy
which includes strict glycemic control prior to the embryonic organogenesis period, or even before in high risk patients. Proper guidance and pregestational genetic exams
are also important. Treatment is a challenge for the doctor
as well as for the parents, and it demands a multidisciplinary approach involving a pediatrician, a pediatric surgeon,
an orthopedic surgeon, a physical therapist and an urologist
depending on the severity. Given the fact that the primary
Figure 4 The lumbar spine magnetic resonance imaging (MRI)
shows an abrupt chord and lumbar termination at the L3 level.
Short spinal cord, flat conus medullaris at T10 level, hypoplastic iliac bones, fused at mid-level. No sacrum is seen.
pathology is irreversible, treatment is just supportive, with
the sole purpose of accomplishing a life as normal as possible.
Funding
References
1. Das SP, Ojha N, Ganesh GS, et al. Conjoined legs: Sirenomelia
or caudal regression syndrome? Indian J Orthop 2013;47:413416.
2. Al Kaissi A, Klaushofer K, Grill F. Caudal regression syndrome
and popliteal webbing in connection with maternal diabetes
mellitus: a case report and literature review. Cases
J 2008;1:407.
3. Boulas MM. Recognition of caudal regression syndrome. Advances in Neonatal Care 2009;9:61-69.
4. Singh A, Kapoor S, Pradhan G, et al. Scoliotic deformity and asymptomatic cervical syrinx in a 9 year old with caudal regression syndrome. J Pediatr Neurosci 2012;7:191-193.
77
5. Singh SK, Singh AD, Sharma A. Caudal regression syndrome case report and review of literature. Pediatr Surg Int
2005;21:578-581.
6. Aslan H, Yanik H, Celikaslan N, et al. Prenatal diagnosis of caudal regression syndrome: a case report. BMC Pregnancy Childbirth 2001;1:8.
7. Fadhlaoui A, Khrouf M, Gaigi S, et al. The sirenomelia sequence: a case history. Clin Med Insights Case Rep 2010;3:4149.
8. Pinter E, Reece EA, Leranth C, et al. Arachidonic acid prevents
hyperglycemia associated yolk sac damage and embryopathy.
Am J Obstet Gynecol 1986;155:691-702.
9. Karacalioglu AO, Soylu K, Emer O, et al. Incidental finding of
sacral hemiagenesis on the 99mTc-MDP bone scan as a casual
regression syndrome type II. Hell J Nucl Med 2008;11:175-178.
medicina
universitaria
www.elsevier.com.mx
Review article
Review of plants with hepatoprotective activity evaluated in
Mexico
L. Torres-Gonzáleza, N. Waksman-de Torresb, J. Pérez-Meseguerb, L. Muñoz-Espinosaa,
R. Salazar-Arandab, P. Cordero-Péreza,*
Liver Unit, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L.,
Mexico
a
b
Department of Analytical Chemistry, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
KEYWORDS
Hepatoprotective
plants;
Hepatoprotective
activity; Extract of
plants; Mexico.
Abstract Liver diseases represent a major health problem around the world. In Mexico these
are the 5 th leading cause of death in the economically active population. In Mexico, it is
estimated that about 60% of the population uses some medicine from plants to treat their
illnesses. The purpose of this work was to search for medicinal plants in Mexico that have been
evaluated for their hepatoprotective effect in different models. In this review we found only 13
plants evaluated for hepatoprotective activity: Amole tuber, Cochlospermum vitifolium,
Heterotheca inuloides, Hibiscus sabdariffa, Leucophyllum frutescens, Prostechea michuacana,
Psidium Guajava, Rosmarinus officinalis, Verbena Carolin, Centaurea americana, Juglans
mollis, Krameria ramossisima and Turnera diffusa. This study describes the studies conducted
in Mexico for each of them and the international literature reports of pharmacological and
phytochemical studies.
Introduction
Liver diseases represent a major health problem around the
world, receiving special attention from health professionals
and scientists. They affect about 10% of the world’s population
and include fatty liver disease, chronic hepatitis, alcoholic
steatosis, fibrosis, cirrhosis and hepatocellular carcinoma.1
In Mexico, such diseases represent the 5th leading cause of
death in the economically active population.2 Studies on liver disease tendencies and epidemiologic projections in
* Corresponding author: Gonzalitos 235, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: (01 81) 8329 4205, (01 81) 8347
6180. E-mail address: [email protected] (P. Cordero-Pérez).
Review of plants with hepatoprotective activity evaluated in Mexico
Mexico predict an increase in the next 2 years, as a result of
the low rate of treatment response which these conditions
present.3-5
Medicinal plants constitute a viable alternative for the
development of phytopharmaceuticals with hepatoprotective activity in order to solve some of these health problems.
Civilizations in countries like China, India and Egypt have
employed this source for thousands of years. In Mexico, the
use of herbal remedies is an ancestral practice, but even
though the information about the plant’s attributed properties is transmitted from generation to generation, for the
most part there is no research supporting the information.6
It has been established that just 20% of the plants used in
traditional medicine have been biologically and scientifically assessed.7 In Mexico, close to 60% of the population uses
some type of remedy based on plants to treat their diseases.8 The use of medicinal plants has been employed by socially and economically disfavored groups, in addition to the
part of the population with cultural and economic resources
who generate an increase in the consumption of medical
plants.9
The purpose of this work was to search for medicinal
plants in Mexico that have been evaluated for their hepatoprotective effect in different models.
In this review, bibliographic research was identified through
editorial books, articles and indexed as well as non-indexed
journals. The indexed articles were found by searching
through PubMed, Medigraphic, Imbiomed, Scifinder and
ScienceDirect, using the following terms: plant extract, hepatoprotective plants, hepatoprotective activity in Mexico.
In addition, non-indexed sources were identified through
health websites and International Health agency reports.
We only considered plants with a detailed description of hepatoprotective activity.
Results
In the present review we found just 13 plants that had been
evaluated for hepatoprotective activity in Mexico, mainly
through in vitro and in vivo studies in experimental hepatic
damage models. We did not find any report of plant hepatoprotective activity in controlled clinical studies in Mexico.
Here is a description of each of the plants which have reported hepatoprotective activity by Mexican research groups in
natural products, as well as some reports from international
literature of pharmacological and phytochemical studies
described for every one of them.
Amole tuber
Agave sp, belongs to the Ruscaceae family, commonly known
as Amole. This is an endemic plant of America, distributed
in the southeast of the United States and the south of Florida up to the tropical area of South America, including the
Caribbean.10-12 Amole tuber (Agave sp.) has been referred to
for the treatment of diseases with a bacterial etiology,
and against diseases associated with oxidative stress (i.e.
cancer, diabetes and hypertension).13-16 On the other hand,
79
antifibrogenic,17 anti-inflammatory,18 antihypertensive,19 inmunomodulator,20 antiparasitic21 and antifungal22 activities
have been reported (Table 1). Even our search only found
one report on the evaluation of the hepatoprotective effect
of Amole tuber. In this study, antifibrogenic activity was
proven on experimental cirrhosis induced by carbon tetrachloride (CCl4) in rats, where a reduction in aspartate aminotransferase (AST) in serum was reported, as well as minor
centrilobular fibrosis, perihepatocytic fibrosis, and minor collagen in the group of rats taking an aqueous extract
of Amole tuber compared to the CCl 4-induced cirrhosis
group.17
Centaurea americana
A species of Centaurea, belonging to the Asteraceae family,
commonly known as American Starthistle or American Basketflower is an annual plant, native from the north of Mexico, Coahuila, Nuevo León, Arizona, Arkansas, Kansas,
Louisiana, Missouri, New Mexico, Oklahoma and Texas and
cultivated in several countries. It has been referred to by
“healers” in the treatment of liver diseases.23 The characterization of this plant has generated the isolation of sesquiterpene, lignans and phytoecdysteroids.24,25
There are 4 studies of interest on this species.23-26 In one
of them, antioxidant activity and toxicity were evaluated
through the fatality of Artemia salina from the hexane, dichloromethane and methanol extract of Centaurea americana seeds. Here, the antioxidant activity of methanol extract was good compared to the controls. Regarding toxicity, none of the extract was toxic; however, isolated lignans
from total extracts showed considerable toxicity.24 Antioxidant activity of C. americana has also been evaluated
through the capture of free radicals 1-1-diphenyl and 1-2-picrylhydrazyl through thin-layer chromatography and spectrophotometry, displaying strong antioxidant activity.23 The
anti-tumor activity of lignans obtained from C. americana
was evaluated in another study, which showed that at a 50
mg/6 dosage arctigenin was effective in inhibiting the development of colorectal cancer C38 in mice C57BI/6.26 Lastly,
hepatoprotective activity from the flower and stem/leaf
methanol extract of C. Americana was evaluated in human
hepatoma cells (Huh7) posterior to the damage induced by
CCl4. This damage was measured through cellular viability,
AST release and oxidative stress after malondialdehyde
(MDA) generation. This study shows that pre-treatment of
the Huh7 cells with methanol extract at a 10, 100 and 1000
µg/ml concentration protected the cells from damage induced by the toxic agent.27
Cochlospermum vitifolium
A species of Cochlospermum, from the Bixaceae family commonly known as “Silk cotton tree”. It is a deciduous dry forest tree in Mexico; its bark decoction is used in traditional
medicine for the treatment of hypertension, type 2 diabetes mellitus, hepatitis and related diseases.28 The traditional
drink is prepared using 10 g of dried plant in 1 L of water. In
this plant’s characterization, flavones and flavonoids were isolated, compounds to which biological activity is attributed.29
There are several pharmacological studies related to this species evaluating the plant’s vascular relaxing activity.30,31
80
L. Torres-González et al
Table 1 Plants with hepatoprotective activity evaluated in Mexico.
Plant
Amole tuber
Effects described
Antibacterial, Anti-fibrogenic and
hepatoprotective
Anti-inflammatory
Anti-hypertensive
Immunomodulatory
Antiparasitic
Antifungal
Centaurea americana
Hepatoprotective
Cochlospermum vitifolium
Anti-hypertensive and hepatoprotective
Heterotheca inuloides
Treatment of skin damage
Antimicrobial
Antioxidant
Anti-inflammatory and
Analgesic
Hepatoprotective
Hibiscus sabdariffa
Juglans mollis
Krameria ramosissima
Leucophyllum frutescens
Prostechea michuacana
References
10*, 11*, 12
17*
18
19
20
21*
22*
23*, 27*
28*
36*
37
38
40
42*
Anti-hyperlipidemic
Anti-hypertensive
Diuretic
Hepatoprotective
45
46
47
50*
Anti-diarrheic
Anti-inflammatory
Anti-oxidant
Antifungal
Hepatoprotective
51
52
53
55
27*
Anti-gastric and intestinal cancer
Not hepatoprotective
57
27*
Treatment of liver and gallbladder disorders
Hepatoprotective
58*
60*
Anti-inflammatory, diuretic, antidiabetic
Hepatoprotective
61*
63*
65*
Psidium guajava
Treatment of gastrointestinal and anti-inflammatory
disorders
Cures jaundice
65*, 66*
Rosmarinus officinalis
Turnera diffusa
Antiseptic
Anti-rheumatic
Anti-inflammatory
Hepatoprotective
Antidiabetic
Anti-ulcerogenic
Anti-depressive
Antioxidant
76
77
78*, 84
78*, 79
80, 81
82
83
80
Treatment of sexual impotence
Treatment of depression
Treatment of inadequate coitus
Antioxidant
Hepatoprotective
87, 89
90
91
23*, 92
27*
Verbena carolina
* Studies performed in Mexico.
Treatment of bile disorders
Hepatoprotective
93*, 95*
In another study, we are able to see that the angiotensin II
receptor is inhibited by more than 50% by this plant’s extract. 32 A 3 rd report showed anti-inflammatory activity
through cyclooxygenase inhibition.33 Finally, in a different
study antidiabetic, anti-hypertensive and hepatoprotective
effects of this plant were reported. Hexane, dichloromethane and methanol extracts were evaluated, and the
hexane extract displayed significant relaxation independent of the endothelium in the rat’s aorta and the methanol extract produced a relaxation dependent on the
endothelium in tissue. In addition, the hexane extract (120
mg/kg dose) showed a significant reduction of glucose levels in rats. On the other hand, the methanol extract (100
mg/kg dose) was also administered in the biliary duct to
determine hepatoprotective activity, showing a statistically
significant decrease in serum AST and alkaline phosphatase
levels.34
Heterotheca inuloides
A species of Heterotheca which belongs to the Asteraceae
family, commonly known as Acáhuatl, Acahual and Arnica. It
grows wild in both cold and warm regions of Mexico.35 Dry
flowers of Heterotheca inuloides have been used for a long
time as a popular medicine in a topical treatment for contusions, bruises and postoperative thrombophlebitis. More frequently this plant has been used externally for skin damage.36 Moreover, it has been recognized as an antioxidant,
for its inhibitor activity against lipid peroxidation and oxidative hemolysis, and for its antimicrobial, anti-inflammatory,
analgesic and cytotoxic effects against several solid tumor
cellular lines.37-40
This plant’s cetonic and methanolic extracts had been
previously characterized, and it is known to have several
constituents such as polyacetylene, cadinales, triterpenes,
sterols, sesquiterpenes, flavonoids and glycosylated flavonoids.41 Its hepatoprotective activity was shown in a toxicity
model by CCI4 in rats. This research proved that animal pretreatment with a methanolic extract of Heterotheca inuloides (100 mg/kg of weight) attenuated the increase in AST
serum activity, alanine aminotransferase (ALT) and histological changes observed in the damage induced by CCl4. Additionally, it was linked to the prevention of stress markers
(oxidative, 4-hydroxynonenal and 3-nitrotyrosine) as well as
activity decrease in several antioxidant enzymes including
superoxide dismutase, catalase and glutathione peroxidase.42
Hibiscus sabdariffa
A species of Hibiscus, belonging to the Malvaceae family,
commonly known as Rosella, Red Tea, Southern Tea or “Rosa
de Jamaica”. This plant is distributed throughout Latin
America, southern Asia, India and areas of central Africa.43
Several parts of the plant, such as leaves, flowers and chalice, have been used as infusions for medicinal purposes.44 It
is commonly used for anti-hyperlipidemic45 and anti-hypertensive effects;46 another use for it is as a diuretic.47 The compounds linked to beneficial effects are polyphenols,
anthocyanins, flavonoids and proanthocyanidins.48,49 This
plant’s aqueous extract is reported to attenuate hepatic steatosis in obese mice. In a study, treatment with an aqueous extract of Hibiscus sabdariffa (administered ad libitum)
81
reduced the accumulation of fatty tissue, decreased weight
and normalized the glycemic index. It also reduced blood
lipid levels in mice compared to the group of obese mice
that did not receive treatment. Moreover, the treatment attenuated hepatic steatosis, through the sterol regulatory
element binding protein 1C and peroxisome proliferatoractivated receptor, interleukin-1 messenger RNA blockade,
tumor necrosis factor-alpha, lipid peroxidation and catalase
messenger RNA level increment.50
Juglans mollis
A species of Juglans belonging to the Juglandaceae family,
commonly known as Walnut, Walnut Tree or Gallic Nut. The
leaves contain hyperoside and other glycosides and flavonoids. Chlorogenic acid, caffeic acid, ferulic acid, sinapic acid,
gallic acid, ellagic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin and juglone have been described in its characterization. Walnut liquor is reportedly used
to prevent low-density lipoprotein (LDL) oxidation and total
cholesterol and LDL cholesterol reduction without change in
high-density lipoprotein (HDL) cholesterol, which reduces
cardiovascular risk.
The leaves are used as an antidiarrheal and as a topical
healer; it has also been reported that they possess antifungal properties and anti-inflammatory and anti-oxidant properties in mice.51-55
In a study, the plant’s antioxidant activity was evaluated
through different assays such as capture of free radical l-ldipheny l-2-picrylhydrazyl via thin-layer chromatography
and spectrophotometry, xanthine oxidase inhibitory activity and total content of phenols. This study showed that Juglans mollis extract displayed a strong antioxidant activity,
through all the evaluated assays.
In a different study, the hepatoprotective effect of the
plant was evaluated in an in vitro model after induced damage by CCl4. Pre-treatment with methanol extract of the
leaf and bark protected human hepatoma cells (Huh7)
from damage induced by the toxic agent, because it
showed decreased AST activity released at the culture medium and lipid peroxidation in comparison to the damage
group.27
Krameria ramosissima
A species of Krameria, belonging to the Krameriaceae family, it is known as Calderona.56 It grows in the northeast
of Mexico and the root is used for medical purposes. There
are reports of its use in stomach and intestinal cancer
treatment and it is used as a tea in case of diarrhea and
moderate fever. Nornelignans 2-(4-hydroxyphenyl)-5- (E)
-propenyl-benzofuran and 2-(2,4,6- trimethoxyphenyl)-5(E) -propenyl-benzofuran have been isolated from this
plant for the medicinal uses previously described.57 The
methanol extract effect of this plant was evaluated in a
human hepatoma cell model (Huh7). In this study it was
proved that the methanol extract was toxic at the evaluated concentrations (10,100 and 1,000 µg/mL) measured by
cellular viability, AST le-vels and MDA production, thus discarding its hepatoprotective activity.27
82
Leucophyllum frutescens
A species of Leucophyllum, belonging to the Scrophulariaceae family. It is known as Texas Ranger, Texas Sage, Cenizo,
Texas Silverleaf or Ash-bush. This plant was originally grown
in Texas, New Mexico and the north of Mexico. Now it is widely grown in Florida and the south of Asia, where it blooms
magnificently in tropical weather. It is used to relieve fever,
cough, asthma and rheumatic pains. It is also used for gallbladder and hepatic disorders.58 A phytochemical study revealed the presence of phytotoxic furofuran lignans called
diayangambin, epiyangambin, diasesartemin, and epiasantin.59 The hepatoprotective effect has been shown in Wistar
albino mice in intoxication with CCl4. This study reported
that methanol extracts of Leucophyllum frutescens (100
and 200 mg/kg) administered orally at 2 ml/kg weight twice
a week for 50 days, decreased hepatic enzyme levels (AST
and ALT) induced by CCl4 damage. In addition, the study
showed maintenance of the hepatocytes membrane’s structural integrity after the methanol extract administration at
both evaluated doses.60
Prosthechea michuacana
A species of Prosthechea belonging to the Orquidaceae family, commonly known as “Water Sweet Potato” or “Water
Lily”. It is an orchid species and is used as an anti-inflammatory, diuretic, antidiabetic agent and for hepatic disorders.61
Characterization studies of this species’ constituents have
been reported to contain 8-C-(6-deoxy-D-glucopyranoside)
apigenin, 1-(3’- hydroxy-5’-methoxyphenyl)-2-(4”-hydroxy-5”-methoxy phenyl) ethanol and malic acid 2-(4-hydroxybenzyl). 62 Hepatoprotective activity was evaluated in a
model of hepatic damage induced by CCl4 and paracetamol
in rats. This study showed that pre-treatment in rats with
methanol extracts at 200, 400 and 600 mg/kg significantly
reduced ALT, AST and alkaline phosphatase levels as well as
total bilirubin in a dose-dependent manner in animals treated with paracetamol and tetrachloride.63
Psidium guajava
A plant of the genus Psidium, which belongs to the Myrtaceae family and is commonly known as guayabo, guayaba or
guayabero. This plant is considered native to Mexico, extending through South America, Europe, Africa and Asia. It
grows in all the tropical and sub-tropical areas of the world,
adapting to the differing climatic conditions but preferring
dry climates.64 Its principal traditional use in Mexico is the
treatment of gastrointestinal, respiratory, and inflammatory
disorders.65 The root, bark, leaves and unripe fruits are
commonly used for the treatment of gastroenteritis, diarrhea and dysentery. Its leaves are applied to wounds and ulcers; they are also used for rheumatic pain, and chewed
they relieve pain in the molars. The decoction in water of
the leaves of this plant is used to cure jaundice and reduce
glucose levels in diabetics.65,66
The antioxidant activity of Psidium guajava is due primarily to the presence of caryophyllene oxide, caryophyllene
and tannins. It has likewise been characterized to contain
constituents such as flavonoids, triterpenes, saponins and
monounsaturated fatty acids, which have been reported
with multiple biological activites.67
The hepatoprotective effect of extracts from this plant
has been evaluated in multiple models. In one investigation,
the aqueous extract of the leaves of Psidium guajava was
studied in the hepatic damage induced by CCl4, monitored
by serum transaminases (AST and ALT), alkaline phosphatase,
serum cholesterol, total lipids and histopathology. The extract
of the leaves at a dose of 500 mg/kg produced significant hepatoprotection.68 In another report, the hepatoprotective activity of this plant was evaluated in the experimental acute
hepatic damage induced by CCl4 and paracetamol in Balb/c
mice. In this study it was reported that the methanolic extracts of the leaves of this plant, at a dose of 250 mg/kg and
500 mg/kg, significantly reduced the serum levels of AST,
ALT, alkaline phosphatase and total bilirubin. The high dose
of the methanolic extract prevented weight increase of the liver when it was compared with the damage control, while
the low dose was inefficient except for the damage induced
by paracetamol. The histological evaluation of the hepatic
tissues showed a reduction in swelling, degenerative changes and steatosis.69
The pre-treatment with Asian acid (a terpenoid extracted
from Psidium guajava leaves and fruit) at doses of 25 mg/
kg, 50 mg/kg or 100 mg/kg significantly hindered the serum
AST and ALT increase induced by lipopolysaccharide and Dgalactosamine; it also showed a decrease in nuclear condensation, proliferation and lesser lipid deposits.70
Rosmarinus officinalis
A plant of the genus Rosmarinus, which belongs to the Lamiaceae family, commonly known as Blessed, White Rosemary, Common Rosemary, Coronary Rosemary, Garden
Rosemary, Fine Rosemary, Female Rosemary, Male Rosemary,
Peregrine Rosemary, Royal Rosemary, Rose of the Sea, Rosmarino or Rumani. It is native to Europe, but is widespread
in Mexico and Brazil. This plant is known for its use in foods,
but it is acquiring interest for its pharmacological properties. Two groups of compounds are primarily responsible for
the biological activity of this plant, the volatile fraction and
phenolic constituents like rosmarinic acid71 and fractions of
flavonoids and diterpenes, which are structural derivatives
of carnosic acid.72-75 It has been utilized for medicinal purposes and is known for its antiseptic,76 anti-rheumatic, antiinflammatory77 and anti-spasmodic properties. The extracts
obtained from this plant have shown hepatoprotective,78,79
antidiabetic,80,81 anti-ulcerogenic,82 antidepressive,83 antibacterial, antioxidant80 and anti-inflammatory effects.84 Its
hepatoprotective effect was evaluated through the induction of acute hepatic damage induced by CCl4 in rats. In this
study the pre-treatment with 200 mg/Kg of Rosmarinus officinalis prevented hepatic lipid peroxidation and increase in
bilirubin and ALT levels; it also prevented the recovery of
the consumption of hepatic glycogen and the increase in
glutathione-S-transferase plasma. The histological evaluation showed a partial prevention of inflammation, necrosis
and vacuolization induced by CCl4.78
Turnera diffusa
A plant of the genus Turnera, which belongs to the Turneraceae family, commonly known as Damiana, Shepherd’s Herb,
Venison’s Herb and Pastorcita.85,86 It is a plant native to
America and Africa; it has a geographical distribution that
extends from Texas to South America; it is wild in the majority of our country, although it is originally from Baja California. It is used in infusions, decoctions, dyes and tobacco.
The best form of utilizing this plant has been described as
employing 4 g of fresh plant into 120 ml of water and drinking it as a tea after meals. This plant is traditionally utilized for the treatment of various illnesses, including sexual
impotency, neurasthenia, diabetes mellitus, urinary retention, malaria, diarrhea, peptic ulcers and alcoholism.87-89
The natives of the north of Mexico have used it to combat
sexual impotency. The Mexican Pharmacopoeia recognizes
that the plant acts as a general tonic and diuretic. The British Herbal Pharmacopoeia lists the specific indication of
Damiana for anxiety associated with impotence and it includes other indications such as depression, nervous dyspepsia, atonic constipation and inadequate coitus.
Phytochemical reports on this plant report the presence of
glycosides, phenolic glycosides, flavonoids, carbohydrates
and volatile oils.90,91 A study showed that arbutin, a major
constituent, is a powerful antioxidant compound.92 Different trials have evaluated the antioxidant activity of this
plant including the capture of free radicals 1-1-diphenyl2-picrylhydrazyl by thin-layer chromatography and spectrophotometry, inhibition of xanthine oxidase activity and
total phenols content. Throughout all these trials it was
shown that the Turnera diffusa extract is a strong antioxidant.23
The hepatoprotection of this plant was evaluated in an in
vitro model through the induction of damage by CCl4. In this
study, it was shown that pre-treatment with the methanolic
extract of the surface of this plant protected that cells from
harm induced by CCl4 at doses of 10 and 100 µg/ml, measured by the AST released at the culture medium, MDA and the
maintenance of cellular viability.27
Verbena carolina
A plant of the genus Verbena, which belongs to the Verbenaceae family, commonly known as the Saint Joseph’s Herb,
Saint John’s Herb, Verbena, Dog’s Verbena, Fieldspike,
Black Pennyroyal, Large Wormwood and Chinese Chili.93,94
Widely distributed in the Valley of Mexico with the exception of the northeast where its occurrence becomes sporadic. It grows from Arizona to El Salvador and Honduras. In
traditional Mexican medicine, it is utilized in the treatment
of hepatic illnesses, diarrhea, renal problems and dysentery
as a purgative. It is also employed in molar pain, headaches,
malaria, rheumatism and pyrogenic states; the flowers are
infused by impact and the foliage is used as an infusion for
bile disorders.93 The effectiveness of this species was evaluated in a study in the model of hepatic damage induced by
CCl4 in mice. The CCl4 produced a rise in gamma-glutamyl
transpeptidase serum activity, ALT, alkaline phosphatase,
MDA and total bilirubin concentration, but it decreased hepatic glycogen. Verbena partially avoided the effect of the
CCl4 in the activity of gamma-glutamyl transpeptidase, but
it did not diminish the effect on the other evaluated markers.95
83
Discussion
According to the present revision, there are few plants evaluated for hepatoprotective activity in Mexico. In most studies, hepatoprotective activity has been evaluated in in
vitro and in vivo experimental models with different inductors of hepatic damage.
No controlled clinical studies on the use of extracts of
natural products in patients with some type of hepatopathy
were found; this contrasts with the many international studies reporting the use of different standard or compound
isolated herbal extracts for the treatment of hepatic diseases.
The goal of most plant extract studies is the development
of phytopharmaceuticals with hepatoprotective activity for
the treatment of diseases such as fatty liver, hepatic diseases caused by alcohol and as a factor in viral hepatitis. In
this context, isolation and characterization of the main
compounds of the active extract are crucial steps in the development of a new phytopharmaceutical. This is essential
to guarantee the active principles within, as well as for the
phytopharmaceutical’s quality control issues. Even though
there are other non-scientific reports describing hepatoprotective activity of several plants in Mexico, there are no in
vitro or in vivo studies which support this activity; thus the
importance of the present review where only 13 studies
were found among national and international scientific literature of plants with hepatoprotective activity evaluated in
Mexico. The need to conduct experimental and clinicallycontrolled studies for the use of plant extracts with hepatoprotective activity is highlighted as a result of their high
consumption among the Mexican population and the secondary
effects that may occur, which may cause hepatic damage.
Funding
This work was support by SEP-CONACYT 2012-CB-201201180977.
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medicina
universitaria
www.elsevier.com.mx
Expert’s corner: a personal approach
Fear of the unknown: Influenza vaccination
J. G. Velasco-Castañóna,*, C. E. Medina-De la Garzaa,b
Centro de Investigación y Desarrollo en Ciencias de la Salud, (CIDICS) Universidad Autónoma de Nuevo León, Monterrey, N.
L., Mexico
a
b
Department of Immunology, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: March 2014; Accepted: April 2014
Immunization -whether from polio, typhoid, flu or whooping cough- is never absolute. A shot in the arm may save
your life -but you can’t always rely on it… Nor is any immunization absolutely safe.1
Influenza is a major cause of morbidity and mortality; current estimates by the World Health Organization (WHO) are
3 to 5 million cases and 250,000 to 500,000 deaths worldwide every year.2 Most deaths associated with it occur among
people age 65 or older, as well as among persons suffering a
chronic debilitating disease regardless of age. The recent
2009 pandemic served to foster interest in this disease.3
An inactivated virus vaccine has been available since the
late 1940´s but it only began to be used extensively when
the influenza virus antigenic variability was taken into account. Aside from such variability, influenza viruses are capable of infecting a wide variety of vertebrates,4 including
many avian species, both wild and domestic, thus it is essential to monitor the antigenic characteristics of influenza virus
strains currently circulating, and so the vaccine formula has
to be evaluated and modified accordingly every year.
Vaccine indications
The efficacy of influenza vaccine is relatively low (70%-90%)5
and vaccinated persons could have insufficient protection
even to homologous virus strains, not to mention those
viruses that have undergone antigenic changes, either drift
or shift. Furthermore, other respiratory viruses such as parainfluenza, adenoviruses or respiratory syncytial virus
could cause a similar illness, frequent anecdotal comments
of acute respiratory illness (ARI) coincident with vaccine
application is therefore not too surprising.
The risk of complications during an influenza episode, leading to hospitalization and death is higher in older people
(≥ 65 years) and in those patients undergoing any of a wellknown list of chronic debilitating diseases,6 yet the benefit
of the influenza vaccine should be weighted in different situations. In Mexico, the Ministry of Health (Secretaría de
Salud) recommends vaccine application to people belonging
to certain groups7 (Table 1).
Additional information to make better particular recommendations for influenza vaccine use is available from
WHO,8 as well as from the Advisory Committee on Immunization Practices9 in the United States of America:
• Healthy individuals: vaccination may be recommended from age 50 onwards.
• Adults and children with health conditions such as
chronic pulmonary disease (including asthma) or
cardiovascular (except isolated hypertension), renal, hepatic, neurological, hematologic, or metabolic disorders (including diabetes mellitus).
• Persons who have immunosuppression, including compromised immune systems caused by
* Corresponding author: Centro de Investigación y Desarrollo en Ciencias de la Salud, (CIDICS) Universidad Autónoma de Nuevo León. Carlos Canseco s/n and Av. Gonzalitos, Mitras Centro, C.P. 64460, Monterrey, N. L., Mexico. Telephone: 1340 4370 (J. G. Velasco-Castañón).
88
J. G. Velasco-Castañón and C. E. Medina-De la Garza
Table 1 Groups considered a priority to get influenza vaccine, Ministry of Health (Secretaría de Salud), Mexico, 2014.
Contagion risk
Individual risk
Population characteristics
High
Low
Health care personnel
Low
Low
General (healthy) population
Age
Children aged 6 months to 5 years, and people over 60
Low
High individual
risk from
medical
complications
Debilitating conditions
Any adult suffering obesity, diabetes, chronic lung disease,
heart disease, HIV-infection or cancer
Pregnancy
Women in any trimester of pregnancy
Adapted from Ministry of Health, Mexico.7
tecnico_influenza.pdf
•
•
•
•
http://www.epidemiologia.salud.gob.mx/doctos/lineamientos/influenza/documento_
medications or human immunodeficiency virus
(HIV) infection.
Women who are or will be pregnant during the influenza season.
Children and adolescents (aged 6 months-18 years)
who are receiving long-term aspirin therapy
and who might be at risk for experiencing Reye’s
syndrome after influenza virus infection.
Residents of nursing homes and other long-term
care facilities.
Persons who are morbidly obese, with a body mass
index (BMI) over 39.
Vaccine use and its public perception
Annual vaccination should take place ideally before the “flu
season” starts, that is, the months of September-October of
each year; if uptake in this period is missed however, later
vaccination is always encouraged, especially for persons at
risk.
Although influenza vaccine is recommended by the WHO
and is firmly established worldwide as an effective measure
for influenza control, the number of persons who receive
influenza vaccine each year is very low even in countries
with good health systems.6,9 Fear of adverse effects has discouraged public vaccine acceptance ever since Edward Jenner first proposed systematic smallpox prevention through
cowpox immunization. The roots of this universal phenomenon are myths and misinformation such as beliefs of vaccine
being the cause of disease, lack of vaccine efficacy, refusal
to get medical care, or plain mistrust of the health care
system. A combination of these factors results in deficient
vaccine coverage.
Data on factors influencing vaccine uptake, such as age,
gender, co-morbidity, educational level, income and area of
residence are important. However, recent research provides
an insight on the reasons for vaccination acceptance or rejection; an improvement on vaccine acceptance requires a
significant level of knowledge and understanding of health
beliefs, attitudes, perceptions and subjective experiences
both on individual and collective levels. This is particularly
evident in older people, who decide to be vaccinated based
on the interpretation and evaluation of beliefs about
whether it could cause or prevent colds and influenza, and
the importance of side effects. Older people’s subjective
assessment of their own health is often incongruent with
objective assessment.10
A group of police, fire fighters and prison workers in Spain,
regarded as essential community workers, surveyed by Caballero et al.11 showed that the vaccine was better accepted
by those who never had doubts about vaccine safety.
In 2009, the Ministry of Health in France purchased 94
million vaccine doses to ensure the vaccination of 65 million
citizens. Yet, there was a low uptake of the vaccine that
could have been related to a lack of high quality advice
about the benefits of getting vaccinated; the same study
also postulated that media and social networks may have
contributed to raise undue concerns in the population. Participation of general practitioners may help to improve vaccine perception by providing face-to-face professional
advice and information.12
Considerations for improvement
Many countries show vaccine uptake rates less than 50% in
health care workers (HCW). Livni et al. found the overall
vaccination rate among a group of pediatric HCW in Israel
was 46.8%. Their data show that knowledge about the
influenza vaccine by health care personnel leads to better
vaccination rates.13
Blasi et al. suggest improving communication between
health authorities, scientific societies, HCW and general population through simple, clear, honest and straightforward
messages to ensure unbiased information about the vaccine
is the basis for a person to accept it.14
Septimus et al. established a mandatory vaccination program for HCW aimed to foster patient safety, including categories for professional employees with patient care (clinical)
duties as well as any other person who could be in the premises. The basis to establish these categories are: 1) access
to clinical areas, and 2) work area within a 2 meter distance
from the patient.15
Influenza vaccination rates are particularly low among
marginalized, hard-to-reach urban populations, so intervention activities are to be designed with a high degree of interinstitutional cooperation, taking into account neighborhood
particularities, strong community organization, and individual orientation.16
Probabilistic models have the power to handle large
amounts of data; these models are also suited to analyze
Fear of the unknown: Influenza vaccination
89
Funding
References
Figure 1 Graphic depiction of fear elicited by smallpox vaccination in 1802. Painting by James Gillray (1756-1815). Image
downloaded from the United States Library of Congress’s Prints
and Photographs division under the digital ID cph.3g03147.
This artistic work belongs in the Public Domain according to
World Trade Organization Agreement on Trade-Related Aspects
of Intellectual Property Rights (TRIPS), 1994.
factors such as weather (low temperature, humidity, and
rainfall), which has been widely anecdotically considered as
associated with seasonal variation of ARI and influenza, and
to enable better decision making, vaccination campaign
planning and resource allocation during epidemics.17
American Indians and Alaskan Natives are also groups targeted for influenza vaccination in the United States of America, so we propose to study the benefits of preventing
influenza in Mexican and other Meso-American ethnic
groups.
As we know from the past, fear and concern about vaccine safety have been present from the beginning of vaccination during the 19th Century (Fig. 1). With an ever-increasing
amount of internet and social network users, anti-vaccination messages lacking scientific foundation may keep the
public at large ill-informed and scared. HCW should
be the best-informed group, with a solid knowledge of vaccination benefits and side effects. Vaccine perception
should not be a black and white picture, but rather a balance between the many benefits obtained contrasted with a
number of known and expected adverse effects. We have
long postulated that a sound application of any vaccine has
to be a carefully crafted benefit vs. risk evaluation, in other
words, adverse reactions are to be considered the lesser evil18 given the higher hospitalization and death rates
among high-risk groups.
1. Furnas JC. So you think you’re immune! Saturday Evening Post
1954;227:38-98.
2. Accessed on March 2014. http://www.who.int/mediacentre/
factsheets/fs211/en/
3. Velasco Castañón JG. El affaire A/H1N1: de un brote epidémico a
pandemia. Medicina Universitaria 2009;11:87-88.
4. Velasco Castañón JG, Medina de la Garza CE. Influenza aviar: La
necesidad de estar preparados. Medicina Universitaria 2006;8:13.
5. Kilbourne ED, Arden NH. Inactivated influenza vaccine. In: Plotkin and Orenstein, Vaccines. 3rd Edition. USA: WB Saunders;
1999. p. 531-551.
6. World Health Organization. Vaccines against influenza. WHO
position paper. Weekly Epidemiological Record. 2012;87:461476.
7. Accessed on March 2014. http://www.epidemiologia.salud.
gob.mx/doctos/lineamientos/influenza/documento_tecnico_
influenza.pdf
8. Accessed on March 2014. http://www.who.int/influenza/vaccines/en/
9. Grohskopf LA, Shay DK, Shimabukuro TT, et al. Prevention and
control of seasonal influenza with vaccines: recommendations
of the Advisory Committee on Immunization Practices - United
States, 2013-2014. Morbidity and Mortality Weekly Report
(MMWR) 2013;62(RR07):1-43.
10. Ward L, Draper J. A review of the factors involved in older
people’s decision making with regard to influenza vaccination:
a literature review. Journal of Clinical Nursing 2008;17:5-16.
11. Caballero P, Tuells J, Duro-Torrijos JL, et al. Acceptability of
pandemic A(H1N1) influenza vaccination by essential community workers in 2010 Alicante (Spain), perceived seriousness and
sources of information. Preventive Medicine 2013;57:725-728.
12. Nougairède A, Lagier JC, Ninove L, et al. Likely correlation between sources of information and acceptability of A/H1N1 swine-origin influenza virus vaccine in Marseille, France. PLoS One
2010;5:1-9.
13. Livni G, Chodik G, Yaari A, et al. Attitudes, knowledge and factors related to acceptance of influenza vaccine by pediatric
healthcare workers. Journal of Pediatric Infectious Diseases
2008;3:111-117.
14. Blasi F, Aliberti S, Mantero M, et al. Compliance with anti-H1N1
vaccine among healthcare workers and general population. Clinical Microbiology & Infection 2012;18(suppl 5):37-41.
15. Septimus EJ, Perlin JB, Cormier SB, et al. A multifaceted mandatory patient safety program and seasonal influenza vaccination of healthcare workers in community hospitals. JAMA
2011;305:999-1000.
16. Coady MH, Galea S, Blaney S, et al. Project VIVA: a multilevel
community-based intervention to increase influenza vaccination rates among hard-to-reach populations in New York City.
Am J Public Health 2008;98:1314-1321.
17. Costilla-Esquivel A, Corona-Villavicencio F, Velasco-Castañón
JG, et al. A relationship between acute respiratory illnesses
and weather. Epidemiology and Infection. Epidemiol Infect 2013;2:1-9.
18. Velasco C. México ante el mundo: La reciente pandemia de influenza. Medicina Universitaria 2010;12:248-249.
medicina
universitaria
www.elsevier.com.mx
Voices of doctors and patients
Between the rose and the shoulders of giants
R. Garza-Mercado*
Department of Neurosurgery, “Dr. José Eleuterio González” University Hospital, Monterrey, N. L., Mexico
Received: August 2013; Accepted: January 2014
KEYWORDS
Juliet Capulet;
Newton; Rose;
Shakespeare;
Shoulders of giants;
Mexico.
Abstract The following are thoughts on 2 of the most well-known phrases in the English
language, recognized as universal academic icons. That of Juliet Capuleto’s in Act II, scene II,
“The Balcony”, in the immortal work of William Shakespeare’s Romeo and Juliet about “A rose
by any other name”, and “On the shoulders of giants”, traditionally attributed to Isaac Newton, the discoverer of the Mechanical Universal Laws, including that of Universal Law of
Gravitation, in the 17th Century, but in reality first said by the humanistic philosopher and
theologist Bernard of Chartres in the 12th Century.
Introduction
People around the world have dedicated time and space in
an attempt to answer the question: “What is the meaning of
a name?1 What does it represent?”. In addition to differentiating one person from another, a name certifies, fundamentally in the Jewish culture, a person’s degree of communion
with spirituality; the concept of “Shem Tov” (good name).2
The Latin phrase Nomen est omen3 “Name is Omen” was an
aphorism which prevailed during the Middle Ages with dogmatic or axiomatic overtones.
But, what about the meaning of phrases? The term “Among
individuals, as among nations, respect for the rights of others
is peace” 4 in Mexico and Latin America immediately
identify Benito Juárez García (1806-1872). Despite Vicente
Fox Quesada’s (1942)5 disrespectful logorrhea, there are
some expressions which, as cosmopolitan icons, are repeated every day in many different languages worldwide. I will
refer to 2 specifically in this work.
Shakespeare’s Rose
English playwright William Shakespeare (Stratford-uponAvon, Warwickshire, United Kingdom, April 26, 1564 - April
23, 1616)6 (Fig. 1), among others, teaches us the value of a
phrase in his greatest work Romeo and Juliet. 7 It is
well-known that Romeo and Juliet is a tragedy in five acts
* Corresponding author: Department of Neurosurgery and Neurological Endovascular Therapy, “Dr. José Eleuterio González” University
Hospital, Universidad Autónoma de Nuevo León. Francisco I. Madero and Avenida Gonzalitos, Mitras Centro, Z.P. 64460, Monterrey, N. L.,
Mexico. Telephone: (+5281) 8346 2698. E-mail address: [email protected] (R. Garza-Mercado).
91
Ta k e n f r o m : h t t p : / / s o b r e i t a l i a . c o m / w p - c o n t e n t /
uploads/2008/07/casa-de-julieta.jpg
Figure 2 Picture of the balcony of Juliet Capulet in Verona,
Italy.
Taken from: http://ageac.org/wp-content/uploads/williamshakespeare.jpg
Figure 1 William Shakespeare (1564-1616).
originally staged in London, England around 1597-1603. Romeo and Juliet tells the story of the passionate love between 16-year-old Romeo Montague, and almost 14-year-old
Juliet Capulet. Briefly summarized, the storyline revolves
around 2 teenagers from Italian families with a long-running
family feud between them; they fall in love with each other
intensely despite their “opposite destinies”, which presages
their love as an “impossibility”.
Wishing to see Rosaline, Romeo attends a ball at the Capulet house in Verona; instead he ends up meeting Juliet.
Romeo recognizes his passionate love for Juliet; they love
each other, so she agrees to secretly marry him. Still inflamed with love after the ball, he sneaks into the Capulet orchard and overhears Juliet at her window vowing her love to
him in spite of her family’s hatred of the Montagues during
Act II, Scene II “The Balcony” (Fig. 2).
Shakespeare utilizes the concept of the rose, the flowery
symbol of lovers. Expressing her love in apparent solitude in
a moaning soliloquy, Juliet rhetorically asks the shining
moon: “What is in a name? That which we call a rose, by
any other name would smell as sweet”.8 Hidden under the
balcony, Romeo makes himself visible to Juliet’s eyes, telling her: “Call me but love, and I’ll be new baptized; henceforth I never will be Romeo”. Friar Lawrence secretly
marries them next morning.
After spending the night with Juliet, Romeo walks the
streets of Verona in the company of his good friend Mercutio. An altercation emerges when they run into Tybalt; Romeo refuses to fight Tybalt since they are now kinsmen.
Mercutio is incensed by Tybalt’s insolence, and accepts the
duel on Romeo’s behalf. In the ensuing scuffle, Mercutio is
fatally wounded when Romeo tries to separate them. Romeo, angered by his friend’s death, pursues and slays
Tybalt, then flees. Meanwhile Juliet’s parents try to force
her into marrying Paris in 3 days. How to avoid this? Following Friar Lawrence’s advice, Juliet drinks a drug which
will put her into a death-like coma for 42 hours, enough
time to inform Romeo, so when he is back in the city they
can face the future together. The messenger, however, does
not reach Romeo. Romeo instead learns of Juliet’s “death”;
grief-stricken, he buys poison from an apothecary, returns
to Verona in secret, and visits the Capulet crypt. He encounters Paris, who has come to mourn Juliet privately. Paris
confronts Romeo, believing him to be a vandal, and in the
ensuing battle Romeo kills Paris. He then looks at his lover’s
“dead body” and drinks the poison to commit suicide. Juliet
then awakes and when she sees Romeo, she stabs herself in
the heart with her lover’s dagger. That is how we remember the text, the theatrical version and the movie (1968,
Dino de Laurentiis, producer, Franco Zeffirelli, Director; Olivia Hussey, Bonaerense, and Leonard Whiting).9
“On the shoulders of giants”
Another reflection which has been perpetuated throughout
the history of science is the following: “If I have seen further, it is by standing on the shoulders of giants”.10 This
expression denotes the greater perspective that one may
have when lifted up and borne aloft on giants. It is evident
when we look at current scientific, cultural and artistic advances that they rest on the revision, repetition, verification and improvement of past findings.11 If true, to validate
and improve, and if false, to point them out as outdated
fallacies.
It was not rare to characterize the ancient as giants and
the modern as dwarves in medieval literature. 12 History
92
R. Garza-Mercado
teaches us that progress in democracy, society and freedom, as well as ethics, bioethics and philosophy, brings a
concatenated change of renewed scientific paradigms and
philosophical or ethical advances, which have universally
led to a better view of the economic, legal, social and political order of towns and their people.13
Strangely enough, it wasn’t uncommon to hear my father
recite the “On the shoulders of giants” phrase around the
house when I was young; however, it seems to have taken a
new meaning after repeatedly hearing it during my residency years in neurosurgery (1957-1961) at the University of
Galveston Texas, from Dr. Samuel Robert Snodgrass (Steubenville, Ohio, March 17, 1906 - Galveston, TX, 1975).14
Back in Monterrey as a neurosurgery teacher for the UNL
(later Universidad Autónoma de Nuevo León, UANL by its
Spanish acronym), I got used to sharing the giant expression
in the classroom with my undergraduate and graduate students. Some of them are currently occupying highlevel political and administrative positions of the State and
the University. After all, and following Aristotle’s thinking
(384-322 B.C.),15 the teachers’ desire is to see themselves
surpassed by their students, feeling a “small” or “big” part
of their success.
Sir Isaac Newton
The phrase “On the shoulders of giants” is traditionally attributed to Isaac Newton, the physics, optics, calculus and
alchemy genius and English astrophysicist (Woolsthorpe,
Lincolnshire, England, December 25, 1642 - London,
England, March 20, 1727).16 Newton (Fig. 3) was also a philosopher of science, a microscope and telescope innovator,
and a theologian. He was also Warden and then Master of
the Royal Mint in 1696, knighted by the Queen in 1705 and
president of London Royal Society for the Improvement of
Natural Knowledge (1703-1727), 17 which was founded in
1660 by 12 English cosmologists with the empiricist motto
Nullius in Verba18 (which means take nobody’s word for it).
Victim of what probably was an involuntary mercury intoxication, Newton died in Kensington/London; he was 85
years old. Because he rejected the enigma of the Holy Trinity, he was denied the ecclesiastic sacrament of extreme
unction. His grave is located in Westminster Cathedral, close to his compatriot Charles R. Darwin (1809-1882); 2 men
without royal blood buried worthily among kings.
Newton’s Magnus Opus -called by many “the best scientific work of all time”- was Philosophiae Naturalis Principia
Mathematica (Fig. 4), which appeared in London on July 5th,
1687 in Latin. His scientific recognition fundamentally rests
in stating that any 2 bodies in the universe attract each
other with a force that is directly proportional to the product of their masses and inversely proportional to the square of the distance between them, known as the Law of
Universal Gravitation.19
True or not, history romantically dictates that this law
was created after an apple fortuitously fell from a tree and
hit him on the head on a summer afternoon in his house
garden.20 The apple, incidentally, is a fruit which plays a
significant role in other famous texts: The Bible (Adam and
Eve), Greek Mythology (the discord, from the Heréspides),
and Snow White.
Taken from: http://www.hyperkommunikation.ch/personen/
newton.html
Figure 3 Sir Isaac Newton (1642-1727) in 1689 by Godfrey
Kneller (1643-1723).
Newton’s life was full of scientific disputes, mainly with
his compatriot Robert Hooke (1635-1703) and the German
Gottfried Leibnitz (1646-1716), caused by the priority of the
gravitational and integral calculus, respectively.
Robert Hooke
Author of the poly-themed Micrographia (1665), Robert
Hooke21 discovered the Law of Elasticity, invented the balanced spiral spring for watches and a microscopic compound which he used to prove the architecture of certain polyhydric cavities constitutive of wood and cork which
he called cells. He was the founder, secretary and lifelong
director of the Royal Society and literature credits him as
the first one to mention the cosmological distances of the
square mechanics, despite the fact that the wise English
microscopist could never pose it as a real scientific theory
of universal attraction, as Newton did.
“If I have seen further, it is by standing on
the shoulders of giants”, 1675
After Principia, Hooke confronted Newton publicly, claiming
priority over the Law of Universal Gravitation, an honor
which, “due to lack of evidence”, was denied by the Royal
Society and the scientific world. Going beyond Royal Society
Taken from: http://twistedsifter.files.wordpress.com/2012/01/
newtons-principia-mathematica-original-book.jpg
Figure 4 The first page of the first edition of Principia, London, 1687.
boundaries, the affray was popularly known reflecting on
its seriousness. Some members suggested to Newton that
he come to terms with his Chamber colleague, advice which he
accepted, or at least appeared to.
In a “respectful” epistle dated February 5, 1675,22 Newton
informed Hooke “as reconciliation” that the reason he was
able to see further was because “he was standing on the
shoulders of Giants”. Literature lucubrates on Newton’s use of
an upper-case G to refer to giants, since ironically Hooke was
“short, hunched, small, and his body was arched like the back
of a G”.23 It is believed that Hooke chose to ignore the sarcasm
or he didn’t get it,24 or maybe it simply did not exist. The impact of this phrase, publicized in London in 1675, was so great
that in the minds of the citizens of the United Kingdom
and the world to the present day, Newton was its creator.
People believe that this phrase about the shoulders of
giants was Newton’s way of paying due homage to the astrophysicists before him: Nicolaus Copernicus (1473-1543),
Tycho Brahe (1546-1601), Galileo Galilei (1564-1642), Johannes Kepler (1571-1630) and famous philosopher René
Descartes, author of the famous phrase Cogito, ergo sum -“I
think, therefore I am”- (1596-1650), and their scientific research methodology.
John of Salisbury and Bernard of Chartres (12th
Century)
Experts, however, have discovered that Newton’s “gigantic”
epistolary expression to Hooke during the 17th Century was
not original, for it was found c. 1130 (about 500 years before Newton) in the voice of French Neo-Platonist philosopher
Bernard of Chartres (1080-1130) a theology professor in the
renowned Cathedral School of Chartres, France.25 This piece
of information was collected from the play Metaligicon,
written in 1159 by one of the most brilliant of Chartres’
disciples, British theologian and scholar John of Salisbury
(Salisbury, England, 1115 - Chartres, France, 1180).26 The
school of Chartres was founded in 990 by Bishop Fulbert of
Chartres (960-1028).27
93
John of Salisbury was an educator, author, diplomat and
philosopher who served as the secretary of the archbishopmartyr of Canterbury cathedral, Saint Thomas Becket (11181170), and was bishop of Chartres (1176-1180). Somewhat
paradoxically, John used to describe himself as John Parvus
-“Little” John-.
Other experts found that at least 4 authors utilized the
“On the shoulders of giants” phrase during the Renaissance
(the 15th and 16th Centuries). Among them, clergy Friar Diego de Estrella (1524-1578) in 1578, and 3 English writers and
poets: John Donne (1572-1631) in 1625, George Hakewill
(1578-1649) in 1627 and Robert Burton (1577-1640) in 1624.
However, it is also cited in literature with a remonstrative
tone. Pedagogue Juan Luis Vives (1492-1540)28 defiantly expressed during the 16th Century; “Not dwarves nor giants,
everybody the same height”.29
Final comments
Referring to the aforementioned “On the shoulders of
giants” in the university classroom, I intended to motivate
my undergraduate and postgraduate students to employ
their best effort and greatest tenacity to learning and in the
selection of appropriate words to express it. After all,
knowledge cannot be acquired via chemical transmutation
or miraculous spiritualization. Neither can it be acquired
by osmosis or inheritance (sorry Darwin). It is the natural
result of daily tenacious effort in the easy (or difficult) art
of learning to learn and teaching to teach. In such tenacity,
the investigator, at any age -old or young- may be rightfully
aided by those who have preceded him on the path, whose
footprints have been verified as trustworthy, useful and
true.
Like runners against the clock, we must aspire to be the
best, setting a goal and fixating ourselves on a time and a
destiny. If the number of neurons is the same in all the normal brains in the world, it becomes necessary to exercise it
and it is not difficult to try to strengthen the baggage of
principles and virtues which the pupil brings with him to
develop in the benefit of the sick.
“The brain” Dr. Ricardo Salinas Ruiz noted philosophically
in one of his commentaries, “is the only organ in the human
body which grows without an increase in volume”. If physical exercise is desirable, cerebral gymnastics are also necessary and essential for the invigoration of thought.
The traditional fallacy Magister Dixit 30 like astrology,
waxed and waned in the darkness of the Middle Ages, making
way for the Nullius in Verba in the 17th Century,18 represented
in the 4 “I´s” of knowledge: Intend, Imitate, Innovate, Invent.31
To the writer, the student-teacher binominal is a logical
2-way street: some learn from others, but rarely does the
teacher discover, in some question or answer of the student,
an unexplored avenue, or the student may warn of an inadvertent inaccuracy in the teacher’s discourse. While it is
true that autodidacts may exist that do not require a teacher to learn (like José Eleuterio González) it would be impossible to imagine a professor without students. Anchylose
thoughts are not profitable. If the words are thrown to the
wind, let us draw near to Publish or Perish,32 required reading for teachers in North American universities.
94
R. Garza-Mercado
Stephen Hawking and others
References
In the real world, one giant in physics and astronomy is British scientist Stephen Hawking, born in Oxford in 1942.33
Hawking -one of the most brilliant minds that have existed
in this world throughout time- is, without a doubt, the supreme illustration that there is no impediment except that
which each person imposes on themselves. As is known, the
Oxford professor is “incapacitated” by amyotrophic lateral
sclerosis (Fig. 5), requiring a wheelchair to move and a voice synthesizer to communicate. Since the diagnosis of his
ailment in 1963, he has offered more than a hundred conferences and written a score of books via dictation. One of his
more recent works was “On the Shoulders of Giants”, in
2003.34
Also recently, the American sociologist Robert King Merton
(1910-2003)35 in 1990 and the British historian of culture Peter Burke (1937)36 in 2012 have referred to “On the shoulders of giants” in their written works. Burke qualified the
phrase as “Very important for the introduction and defense
of modern scientific thinking”, and he warned of the risk
that is run when a “giant of information” could turn into a
“dwarf of knowledge”. We believe that, no matter how vast
or penetrating our view from the heights, we must never
lose sight of the ground of the reality that sustains us. Extraordinariness in our fantasy should be far from imposing
smallness in judgment, fortitude, prudence, strength and
justice.
1. Accessed on March 2014. http://www.es.chabad.org/library/
article_cdo/aid/819494/ jewish/Que-hay-en-un-nombre.htm
2. Accessed on March 2014. http://serjudio.com/rap1401_1451/
rap1438.htm
3. Accessed on March 2014. http://blog.agirregabiria.
net/2007/09/nomen-est-omen-el-nombre-es -el-destino.
html
4. Accessed on March 2014. http://www.frasescelebresde.com/
el-respeto-al-derecho-ajeno-es-la-paz/2/
5. Accessed on March 2014. http://www.proceso.com.
mx/?p=348230
6. William Shakespeare. The New Encyclopedia Britannica. 15th
Edition. Chicago/London: 1994. p. 690-691.
7. Romeo y Julieta. The New Encyclopedia Britannica. 15th Edition. Chicago/London: 1994. p. 163-164.
8. Accessed on March 2014. http://www.bartleby.com/70/3822.
html/
9. Accessed on March 2014. http://www.imdb.com/title/
tt0063518/?ref_=nv_sr_2
10. Accessed on March 2014. http://instintologico.com/sobre-lafrase-de-newton-a-hombros-de-gigantes-y-el-mal-genio-delgenio/
11. Accessed on March 2014. http://ciencialmr.blogspot.
mx/2008/09/la-metodologa-cienti fica.html
12. Debate sobre los antiguos como gigantes y los modernos como
enanos (http://educa cionyentorno.blogspot.mx/2013/04/ahombros-de-gigantes.html).
13. Accessed on March 2014. http://plato.stanford.edu/entries/
progress/
14. Accessed on March 2014. http://neurosurgery.org/society/bio.
aspx ?MemberID=7541
15. Accessed on March 2014. http://www.biografiasyvidas.com/
monografia/ aristoteles/
16. Isaac Newton. The New Encyclopedia Britannica. 15th Edition.
Chicago/London: 1994. p. 663.
17. London Royal Society for Advancement of Knowledge. The New
Encyclopedia Britannica. 15th Edition. Chicago/London: 1994.
p. 220.
18. Accessed on March 2014. https://blogs.otago.ac.nz/emxphi/2012/02/nullius-verba-nihil-verbis-sapere-aude/
19. Ley de la gravitación universal. The New Encyclopedia Britannica. 15th Edition. Chicago/London: 1994. p. 663.
20. Accessed on March 2014. http://actualidad.rt.com/actualidad/view/6088-La-historia-re al-de-manzana-de-Newton-salea-luz-por-primera-vez
21. Robert Hooke. The New Encyclopedia Britannica. 15th Edition.
22. Accessed on March 2014. http://timpanogos.wordpress.
com/2007/12/26/quote-of-the-moment-newton-giants/
23. Accessed on March 2014. http://nosolociencia.blogspot.
mx/2005_02 _01_archive.html
24. Accessed on March 2014. http://io9. com/5877660/was-robert-hooke-really-sciences-greatest-asshole
25. Bernardo de Chartres. The New Encyclopedia Britannica. 15th
Edition. Chicago/London: 1994. p. 144.
26. Accessed on March 2014. http://symploke.trujaman.org/index.php?title=Cate gor%EDa:Escuela_de_Chartres
27. John of Salisbury. The New Encyclopedia Britannica. 15th Edition. Chicago/London: 1994. p. 584.
28. Juan Luis Vives. The New Encyclopedia Britannica. 15th Edition.
29. Accessed on March 2014. http://www.elmundo.es/ladh/numero96/dichosyhechos.html
30. Diccionario de la lengua española (DRAE). 22ª Edición. Madrid:
2001.
Taken from Google® Images.
Figure 5 The astronomer Stephen Hawking (1942) and his amyotrophic lateral sclerosis.
31. Accessed on March 2014. http://www.formulatv.com/noticias/18335/fabrica-de-ideas-de-rtve-regresa-viernes-la-2-tercera-temporada/
32. Accessed on March 2014. http://academia.stackexchange.
com/questions/9173/what-does-pu blish-or-perish-really-mean
33. Stephen Hawking. The New Encyclopedia Britannica. 15th Edition. Chicago/London: 1994. p. 762.
95
34. Accessed on March 2014. http://pjorge.com/2003/06/21/ahombros-de-gigantes -de-stephen-hawking/
35. Accessed on March 2014. http://www.mcnbiografias.com/appbio/do/show? key=merton-robert-king
36. Accessed on March 2014. http://www.emma.cam.ac.uk/teaching/fellows/display/?fellow=49
medicina
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Voices of doctors and patients
The excluded
Marcela Granados-Shiroma*
Research and Development Center in Health Sciences, UANL, Ministry of Health of the State of Nuevo León, Opción
Retorno A.C, Mesa de Paz, Monterrey N.L., México
Received: February 2014; Accepted: February 2014
“Nobody is excluded for what he is, but for the way others
treat him. Maybe there is no excluded individual but only
individuals who exclude.”
Alberto Senante Carrau1
There are “diseases” and events which affect family dynamics and have a large impact on health, stability, communication and relationships within and outside, crossing domestic
boundaries into the community; “diseases” and events that
stigmatize and marginalize those who suffer them, excluding
them from the possibility of a second chance.
Who are the excluded?
In the social concept, when we talk about social exclusion,
we generally think of people or populations entirely lacking
social support, this is the forgotten, mistakenly associated
with almost one single concept: “misery”.
Social exclusion supposes the denial of someone’s right to
be a person. The socially excluded are not granted the most
basic rights, because society does not recognize them and
he/she is not able and/or does not know how to reclaim
them.
Throughout time, different groups have been excluded.
History does not remember them, among these groups there
are: Jews, left-handed people, the mentally-ill, gypsies, artists, poets and painters, people with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome
(AIDS), people suffering from tuberculosis, leprosy, or a disability; homosexuals, drug addicts, delinquents and gang
members suffer from this as well.
Gandhi Peace Foundation’s President Radha Baht, on her
visit to Monterrey, Mexico in December 2011, after spending
time with some gangs, made the following statement:
“In Christ’s time the socially displaced were the lepers,
who were not allowed to live in cities or towns; in Ghandi’s
time, the Pariahs or casteless were the socially relegated;
in Monterrey yesterday I saw the socially rejected, I saw
young gang members. Just as in past times, these young
people are chased, labeled and marginalized from society.”
Exclusive societies vs. positive social
reinsertion
The degree of vulnerability and risk of relapse that people
have after being released from prison or rehabilitation centers for addictions has been addressed in different forums,
when they do not get to a place or environment or people
that may generate and reinforce their wishes to make a positive change towards a free and productive life.
International experience acknowledges that making rehabilitation policies available to citizens gives positive results, not
only in terms of reducing stigmatization among this population (an essential condition for rehabilitation) but also through
the resources that may be attracted through different mechanisms where civil organizations play an important role.
* Corresponding author: Centro de Investigación y Desarrollo en Ciencias de la Salud (CIDICS), Universidad Autónoma de Nuevo León, Av.
Carlos Canseco s/n y Av. Gonzalitos, Mitras Centro, 64460, Monterrey, N.L., México. Email address: [email protected]
(Marcela Granados-Shiroma).
The excluded
The story of Antonio is one of many; he gives a testimony
of a positive social reinsertion, this is, the possibility to reinsert in society, to live with other individuals, respecting
their rights as the main objective.
Antonio was part of a neighborhood gang since he was 8
years old; being a gang member, he took part in all sorts of
activities within and outside the law. Fights with other
gangs were part of his daily routine; the many scars on his
body speak for themselves. He was involved in small robberies all the way up to car theft, which were at first without
violence but resorted to violence later, and on top of this,
alcohol and drug consumption. Antonio was arrested and
held in the Center for Young Offenders, and later jail; because of his behavior, he was in solitary confinement for
long periods of time, until one day he had a conversation
with a person from a civil association, who invited him to
participate in a rehabilitation program. Antonio recalls: “I
had two options, if I accepted integration with that group,
I would be out of solitary. If I said no, well I would be still
in it. Without having the least interest in rehabilitation, I
went to the group. I had my ups and downs, but they never
left me. I felt they cared about me”. Antonio moved forward
in his rehabilitation, completed his sentence, finished high
school and got a Psychology degree; he is currently studying
his Master’s degree abroad. He has participated as a speaker
in various national and international seminars and congresses. Whenever he gets an opportunity to come, he incorporates different activities and workshops, 1@1 Peace, Peace
talks or Alternatives for a life free of Addictions and Violence, where he shares his knowledge, happiness and vision of
an inclusive society.
Ivan is another young man who tells his testimony “I remember as a kid I used to watch airplanes and I would think
I would never have the opportunity to ride one. I used to
live in a neighborhood where drugs, violence, prostitution
and crime were around me, they were part of my environment”. He recalls that when he was a kid, his father bought
him a small toy accordion that he loved to play; he also
liked going outside to play with the other kids from down
the street. His mom and dad used to encourage him to play
his accordion. He comments “One day I was outside my
grandmother’s house with my dad, playing my accordion. I
was about 13 years old, and a kid around my age walked in
front of the house, he was playing the trumpet, he moved
on, but then he came back, talked to my dad, and asked
him for permission to play with me. From that moment on
a great friendship with Erick began, a friendship that is
strong to this day”. “While we talked”, Ivan remembers,
“one day I was playing with a group of friends, Erick was
singing, and a person approached us and after talking for a
while, he invited us to go to a 1@1 Peace meeting, a civil
association which works exclusively with teenagers. We
liked it, we still participate”. Ivan and Erick received help
to enter the Faculty of Music of the Universidad Autónoma
de Nuevo León, Mexico. Ivan has perfected the craft of the
accordion and Erick of singing, creating “Vallenato” –a musical group-; they have participated in various domestic and
international contests. After 3 participations, they won 1st
place in the “Festival de la Leyenda Vallenata” in Valledupar, Colombia; they have participated in other festivals in
New York and Argentina, in addition to being invited to play
with world-renowned groups at several festivals. Currently
97
they teach music and signing and are looking to get funds to
formalize a civil organization called “Chords for Peace”
where they help children, kids, and teenagers find an alternative to a life of violence and addiction through music and
singing, developing skills and integrating them into their life
plan.
Irene shares her experience. At age 9, she and her 3 younger brothers were taken to the Integral Development of the
Family (DIF), because of abuses and violence from their
father and mother. “Mom used to hit us with a belt, a broom
or a tube for any reason or pretext. She treated me as her
slave. Dad did love me, but if he ever treated me nicely or
bought me something, mom would get mad at him, she
would say mean things to him and then, after he left
the house, she would hit me or lock me up, she would call
me a slut, at that age I did not quite understand what was
going on. I remember mom and dad consuming alcohol until
they passed out, and since I was very little, around 7 years
old, I would drink what was left in the bottles of beer and
wine. After they took us to the DIF, I escaped. I was all over
the place, at 11 years old I prostituted myself; I needed to
stay drunk. At 12 years of age I started using drugs”. She
sadly recalls that time of excess, violence and abandonment.
Some relatives placed her in a rehabilitation center; she relapsed 6 times. The last time she was in rehab, she heard
about a civil association which helps people like her, people
who come out of a rehabilitation center and do not have
anywhere to go. She called them and was accepted by Opción Retorno A.C., where she currently lives; she has not relapsed in over a year, the longest time, she mentions. She
restarted her studies, she works and does not miss her therapies; her dream is to have a nice place to live, and the
necessary income to request full custody of her little
brothers.
Paraphrasing Alberto Senante in relation to The Excluded,
we know that by nature, the human species tends to try to
live in a group. If a group does not accept a person or a
group of people, they seek for another group which accepts
them. Therefore, there are no excluded people; there are
excluding groups or societies. So the question is: Which
groups are those people we exclude from joining our groups
or society? People we exclude based on stereotypes of any
nature or prejudice like ethnicity, nationality, gender, age,
disability, social, cultural or economic condition, health,
pregnancy, language, religion, opinions, sexual preferences,
marital status, clothing, tattoos, or any other condition that
we label as unacceptable or intolerable.
This is a very serious problem in Mexico and even more
serious in Nuevo León, so serious that we are suffering its
consequences in general and in particular. The National Discrimination Poll (ENADIS, by its Spanish acronym) 2010, conducted by the National Council for the Prevention of
Discrimination (CONAPRED, by its Spanish acronym) reports
that Nuevo León is the state with the highest segregation
levels by gender, sexual preferences, skin tone and ideology.
The results of the study are shown under the name “Nuevo
León, leader in discrimination”. The main goal of this study
is to obtain statistical data on the dimension of the discrimination problem in our country by entity, taking into account
populations such as the handicapped, ethnic and religious
groups, women and children, homosexuals, people with
HIV/AIDS and addicts, among others.
98
M. Granados-Shiroma
of the Organization of American States, through the Commission of Jurisdictional and Political Affairs, issued recommendations to the government of Mexico on November
16, 2005, referring to exclusion as a serious problem and as
a priority, which must be attended urgently so that the Rule
of Law prevails.
We hope this space serves to reflect on what we are doing
as doctors and health professionals; moreover, we are a part
of a University Community. There is a lot to be done to stop
being exclusive and become true promoters of positive social reinsertion in all areas in which we interact.
Prevention is the inclusion that makes us open and lets us
see a world with better possibilities (Fig. 1).
And you… how do you wish to join?
Figure 1 It symbolizes the insertion of Prof. Vladimir Firpo.
Reference
With the topic “Racism and every other form of discrimination and intolerance in Mexico”, several documents about
this situation are available; in fact, the Permanent Counsel
1. Accessed in March 2014. http://www.buzoncatolico.es/formacion/solidaridad/sensibilizacion/excluidos-sociales-son-invisibles.html
medicina
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Special article
Biobanks: Experience of the School of Medicine and the “Dr. José
Eleuterio González” University Hospital of the Universidad
Autónoma de Nuevo León
M. L. Garza-Rodríguez, J. A. I. Ascacio-Martínez, A. A. Pérez-Maya, D. C. Pérez-Ibave,
D. E. Monsiváis-Ovalle, H. A. Barrera-Saldaña*
Medical Biotechnology Unit, Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universidad
Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: November 2013; Accepted: January 2014
KEYWORDS
Biobank;
Biospecimens
preservation; Clinical
research; Mexico.
Abstract Medical research has greatly benefited from molecular biology and increasingly
relies on tools from the “omics” disciplines (mainly genomics, transcriptomics, proteomics and
metabolomics). The availability of biological samples preserved with high quality standards is a
sine qua non condition for such studies and their repositories are referred to as biobanks. Biobanks
support the transportation, storage, preservation, and initial pathological and analytical
examinations of biospecimens, as well as the protection of relevant information and the comparison
of clinical and laboratory findings. A biobank facility is one of the most valuable tools the
academic medicine organizations can offer to their researchers to improve the competitiveness
of their current and future medical research. It acts as an essential bridge and an effective
catalyst for research synergies between basic and clinical sciences, and it can be potentiated
with efforts to raise funds for acquiring and maintaining cutting-edge analytical infrastructure
to better serve its clinical, pharmaceutical and biotech clients.
Merging assistance and research
Medical research benefits more and more from laboratory
tests which scrutinize patients’ gene pools (genome), sets
of transcripts (transcriptome), protein patterns (proteome),
and metabolite profiles (metabolomics).
When these researches are geared towards discovering
the causes of the leading health conditions -commonly
* Corresponding author: Medical Biotechnology Unit, Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universidad Autónoma de Nuevo León. Madero and Dr. E. Aguirre Pequeño, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: (81) 8329
4173. E-mail address: [email protected] (H. A. Barrera-Saldaña).
100
caused by the effect of multiple and often subtle metabolomic, proteomic, transcriptomic, or genomic alterations
(i.e., single nucleotide polymorphisms), it is necessary to
include in the research protocols a large number of patients, and to ensure follow-up for several years. This is crucial in an attempt to associate the findings at a molecular
level with the prognosis of diseases and their response to
treatment (pharmacogenetics). Therefore, the procurement, preservation, distribution and analytical processing in
optimal conditions of biospecimens (and their associated
information), is key in order to maximize their validity, reach and impact.1
What is a biobank?
The term “biobank” is relatively new. It first appeared in
PubMed during the 90´s, yet it was not until the year 2000
that it became more frequently used.1,2 Biobanks gather,
store, preserve, process and distribute biological samples
and all associated data. The importance of sample preservation has increased in recent years and countries like the
United Kingdom, the United States of America, China, Switzerland, Estonia, France, Japan, Spain, Norway, and Canada
rely on biobanks for large-scale sample preservation.3
Biobank benefits
Thanks to standardized and systemic biospecimens and related data storage, biobanks are accelerating the development of new biotechnological medications, medical devices
and personalized medicine tests. The combination of clinical, demographic, epidemiologic, and genomic information
of populations -on occasion entire populations (as DeCODE
genetics conducts in Iceland), allows us to explore and decipher complex interrelations between genes, the environment
and habits, thus placing us in the path to discover the causes
of multifactorial complex diseases.3
Human biospecimens stored in a biobank may be used to:
a. Identify and validate therapeutic targets (genes
and gene products).
b. Discover cellular mechanisms underlying diseases.
c. Investigate biomarkers associated with certain subtypes of diseases.
d. Group patients based on their genetic characteristics and response to treatment, which allows for
the development of new individualized therapies.
e. Try disease associations with a genetic variation in
genomes of a certain population and compare it to
other populations.
How does a biobank work?
Most of the materials stored in biobanks are specimens derived from human blood and other tissues, along with the donors’ information. The stored samples correspond to patients
who, fully informed and voluntarily, decided to donate them
with the purpose of supporting scientific research properly
approved by the Research Ethics Committee of the participating institutions. Biobanks operate with dual responsibilities; on one hand they have to preserve the biospecimens
and their respective information; on the other hand they
M. L. Garza-Rodríguez et al
are obliged to protect the privacy and confidentiality of
such information, granting access exclusively to authorized researchers under the applicable institutional guidelines.2,4
Personnel working in biobanks offer the following services:
a. Obtaining a signed consent form including the storage of biospecimens.
b. Compiling the necessary information from the donors.
c. Transporting biospecimens in good time and in an
appropriate manner for their preservation.
d. Codifying all relevant information, guaranteeing
confidentiality.
Origins of the Biobank of the School of
Medicine and University Hospital of the
Universidad Autónoma de Nuevo León (UANL)
The Department of Biochemistry and Molecular Medicine
(DBMM) of the UANL’s School of Medicine has been leading
edge in its country in the study of the molecular biology of
various diseases. These studies were made possible thanks
to the collaboration of different departments and services
of “Dr. José Eleuterio González” University Hospital (HUUANL). Among these researches, the first two gene therapy
protocols (for prostate and cervical cancer) carried out in
Latin America stood out over 10 years ago.
Supported by their current infrastructure, the DBMM’s Medical Biotechnology Unit (MBU) has considerable experience
in large-scale biological sample storage, which was created
through a research project in collaboration with the State
Secretary of Health concerning cervical cancer risk factors.
In 2002 almost 5000 samples from voluntary females were
gathered for this project. This and subsequent large-scale biospecimen storage experiences have made evident the
need to have an institutional biobank.
Gradually, this “pilot biobank” initiated at UBM has been
supporting more and more projects and theses of the different departments of the UANL’s HU and Faculty of Medicine.
An innovative idea
Because the development of clinical research in our institution is expanding, the implementation of its biobank is not
only crucial, but a strategic pillar for the aspirations of excellence in effective assistance, research and connection
with pharmaceutical and biotechnological industries. The
implementation of the institution’s hospital biobanks will
allow the preservation of valuable samples for subsequent
analysis.
Visionary tasks
The institution began implementing its biobank so that researchers -distributed over 52 different departments- may
multiply their excellent researches in scientific and technological approaches, meeting international standards (bioethics
included), with a wider reach and preferably connected to
multi-center projects of interest in public and private sectors, domestically as well as internationally.
Biobanks: Experience of the School of Medicine and the “Dr. José Eleuterio González”
University Hospital of the Universidad Autónoma de Nuevo León
The institutional Biobank will include reception, sampling,
extraction, labs and biomolecules analysis areas, massive lowtemperature storage refrigeration of biospecimens, and computational infrastructure for sample and data control, etc.
The Biobank project is being subjected to evaluation for
its possible approval by our institution’s Research Ethics
Committee. Once the Biobank is operating, each researcher
who requests biological sample preservation there will be
required to have the corresponding protocol’s approval letter from said Committee as an essential requirement to store the biological material.
Contribution to regional and economic
development
The proposed institutional biobank will bring social benefits;
having higher quality researches will contribute to the generation of more and better health in the community, while
alliances with more pharmaceutical and biotechnological
industries will contribute to regional and economic development.
At the same time, the project will help create a new era
for clinical research in Latin America, a region that despite
having become one of the most relevant in the research of
new medications and medical devices, has not grown to its
full potential due to the lack of biobanks.
101
Funding
References
1. Kettis-Lindblad A, Ring L, Viberth E, et al. Genetic research and
donation of tissue samples to biobanks. What do potential sample donors in the Swedish general public think? Eur J Public
Health 2006;16:433-440.
2. Cambon-Thomsen A. The social and ethical issues of post-genomic human biobanks. Nat Rev Genet 2004;5:866-873.
3. Kaiser J. Biobanks. Population databases boom, from Iceland to
the U.S. Science 2002;298:1158-1161.
4. Elger BS, Caplan AL. Consent and anonymization in research involving biobanks: differing terms and norms present serious barriers to an international framework. EMBO Rep 2006;7:661666.
medicina
universitaria
www.elsevier.com.mx
Special article
The Anatomy Research Group (GIA) 10 years after its founding:
Past, present and future
R. Morales-Avalos, R. E. Elizondo-Omaña*, S. Guzmán-López
Anatomy Research Group, Department of Human Anatomy, Faculty of Medicine, Universidad Autónoma de Nuevo León,
Received: February 2014; Accepted: February 2014
“It is important to point out that the most brilliant discoveries have been due, not to the knowledge of written logic,
but to that vivid logic that each individual possesses in
their spirit, with which ideas are tilled…”
Santiago Ramón y Cajal
Spanish Neuropathologist
Scientific activity in medicine increases every year. In the
United States of America, many medical schools offer undergraduate students opportunities to participate in research in different areas of clinical and basic medicine.
These opportunities have increased and strengthened the
activities related to medical research.1-6 In Mexico, other
Medical Schools, such as the Universidad Nacional Autónoma
de México (UNAM) and the Benemérita Universidad Autónoma de Puebla (BUAP) have bachelor degree programs in
biomedicine that are mainly oriented towards laboratory research (www.biomedicas.unam.mx; www.minerva.buap.
mx).7,8 At the Universidad Autónoma de Nuevo León (UANL),
during the past 30 years, the School of Medicine has Student
Research Groups in Medicine (GESTIMED) that focus on care
and research in medicine (www.medicina.uanl.mx).9
In 2003, because of the interest of professors and students in developing original scientific activity, the Research
Group in Anatomy (GIA) of the Department of Anatomy was
established. In the years before its formation, the scientific
activity of the department was isolated and characterized
by individual efforts with little productivity with regard to
publications. But thanks to the interest of undergraduate
students and the firm support of Santos Guzman-López,
Doctor of Medicine Head of the Department, the establishment and recognition of the group allowed strategic development and organized growth with a clear objective:
contributing to the solution of problems of different medical specialties through the development of knowledge in
morphology.
The activities of the group are related to the promotion
and dissemination of science and the scientific method with
a focus on humanity and are based on the values of honesty,
respect and confidence. The group´s mission is to contribute to the formation of human resources that can assist in
the development of the institution and in the solution of
problems in society, as well as generate useful knowledge
for human development.
The GIA is currently composed of an enthusiastic group of
professors and undergraduate and graduate students of the
School of Medicine. We are convinced of the transforming
power of permanent training, continuous education, and
teamwork. The GIA is organized as a general research group
with subgroups in areas of interest and common problems.
To date, the subgroups of the GIA are: GIA-Bones and Joints,
GIA-Peripheral Nerves, GIA-Neurosciences, and GIA-Vascular. The group has 64 students (from 2nd to 12th semesters)
integrated and organized in different research lines of the
* Corresponding author: Francisco I. Madero and Avenida Gonzalitos, Mitras Centro, Z.P. 64460, Monterrey, N.L, México. Telephone: +52
(81) 8329 4171. E-mail address: [email protected] (R. E. Elizondo-Omaña).
The Anatomy Research Group (GIA) 10 years after its founding: Past, present and future
Department of Human Anatomy. It currently has 42 publications in peer-reviewed journals, 1 international and 6 national awards in research; 6 of its members have done research
clerkships abroad; 120 oral presentations in basic and clinical science have been offered in congresses, and financial
resources have been obtained through local and international grants; 4 of its professors are members of the National
Researchers System (SNI), and one is the editor of an international medical journal.
There are 6 research lines in the Department of Human
Anatomy that have generated national and international publications, presentations in congresses and associations with
other departments and services, both internal as well as external to the School of Medicine. The main lines of research
are: 1) Morphological studies in anatomical specimens for
use in minimally invasive surgical approaches; 2) morphological and functional study of peripheral nerve injury in murine models; 3) morphological and functional study of global
and focal cerebral ischemia in animal models for pathophysiological study and the application of neuroprotective
agents; 4) the study of the adaptive morphological response
of vascular grafts and its regulation; 5) use of stem cells as
treatment after central nervous system damage in a mouse
model; and 6) morphological changes in aging. It is important to mention that much of the research is designed, proposed, and developed by students, always with the support
of a professor as advisor in the subject area and from a
methodological point of view.
It is noteworthy to mention that the students themselves
have an internal coordination that allows members to support new members in the initial guidance for the conduction
of protocols, motivating their implementation. This way,
solutions have been developed for the immense amount of
work required for the operation of the group. This has been
achieved thanks to the contribution of department professors and external consultants in internal training, and the
support provided for attendance to conferences and courses
at other research institutions.
This year, the GIA celebrates its tenth anniversary with
the presentation of the First Research Symposium on Anatomy entitled “Contributions to the Clinical Practice of
Anatomical Research” at the XXVII National Congress of Medical Research conducted in the city of Monterrey, Mexico
from October 10 to 12, 2013. Faculty advisors from each
line of research as well as student members of the group
103
participated in this symposium. The objective was to demonstrate the involvement of undergraduates in biomedical
research and encourage students to join groups and research projects.
We are confident that the coming years will be marked by
strong and sustained growth, with the maturation of all processes, agreements, and joint projects with researchers
from other departments and services, and from national and
foreign institutions, with the integration of multidisciplinary
teams to better understand, expand, and diversify scientific
knowledge in various areas of the biomedical sciences.
Funding
References
1. Corr PB. Issues in developing the medical scientist, part 4: relationship between academia and the biomedical industry and
the role of industry in developing medical scientist: American
Federation for Medical Research (AFMR). Journal of Investigative Medicine 2005;53:113-115.
2. Crook ED. Issues in developing the medical scientist: introduction to the series. Journal of Investigative Medicine
2004;52:241.
3. Jeffe DB, Andriole DA. A National cohort study of MD-PhD graduates of medical schools with and without funding from the
National Institute of General Medical Sciences´ medical scientist training program. Academic Medicine 2011;86:953-961.
4. McPhaul MJ. Issues in developing the medical scientist, part 2:
Fostering research among medical students. Journal of Investigative Medicine 2004;52:292-295.
5. Crook ED. Issues in developing the medical scientist, part 1: interview with Dr. Robert W. Schrier, MD. J Investig Med
2004;52:242-245.
6. Shapiro B. The United States Medical Scientist Training Program. Clin Invest Med 1997;20:251-254.
7. Accessed on March 2014. www.biomedicas.unam.mx
8. Accessed on March 2014. www.minerva.buap.mx
9. Accessed on March 2014. www.medicina.uanl.mx
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page, Summary (in Spanish), Abstract (in English),
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Example: 10 pages text = 4 graphs or tables (as a whole); 16 pages text = 7 graphs or tables. Don’t deliver
photos of tables.
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articles on clinical or laboratory research, editorials,
Editor accepts items written in English or Spanish.
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should present clearly the purposes, basic procedures,
clusions. Below the summary, include 3 to 10 keywords
using terms included in the Medical Subject Headings of the latest Index Medicus or based in the terminology vocabulary structured by BIREME in the Descriptors in Health Sciences (DeCS).
11. Abstract (in English). It is a correct English translation
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and discussion. Other kinds of articles, as cases reports,
Standards for authors
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the topic. Do not include here data or conclusions
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role in the study or experiments (patients or lab animals, including controls). Identify the methods, equipment (writing the manufacturer name and address in
parentheses) and procedures with enough details to
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18. References to magazines shall be ordered as follows:
19. Torres BG, García RE, Robles DG et al. Complicaciones
tardías de la diabetes mellitus de origen pancreático.
Rev Gastroenterol Mex 1992;57:226-9.
20. References to books or monographs should appear as
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21. Hernández RF. Manual de anatomía. 2ª Edición. México: Méndez Cervantes; 1991: 120-9.
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25. All correspondence related to this publication, including works proposed to be published, should be directed to Subdirección de Educación Continua, Facultad
de Medicina de la Universidad Autónoma de Nuevo
León, Av. Dr. Eduardo Aguirre Pequeño y Madero s/n,
Col. Mitras Centro, C. P. 64460, Monterrey, Nuevo León,
México. Phone numbers: (0181) 8346-1370, 8347-5867
8329-4193; fax: (0181) 8333-6687; Elsevier Editorial
System EES http://ees.elsevier.com/rmuanl/

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

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