"dr. josé eleuterio gonzález" university hospital univers

Transcription

Vol. 16 • Num. 62 • January-March 2014
Vol. 16 • Num. 62 • January-March 2014 • ISSN 1665-5796
SCIENCE AND RESEARCH JOURNAL OF THE SCHOOL OF MEDICINE
AND "DR. JOSÉ ELEUTERIO GONZÁLEZ"
UNIVERSITY HOSPITAL UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN
ONE BIG
evolutionary step
INFILTRATION VS. INSTILLATION
of ropivacaine 7.5% in
radical mastectomies
for postoperative analgesia
MEDICINA UNIVERSITARIA
MATERNAL MORTALITY
and severe obstetric
morbidity in a tertiary
care hospital
www.elsevier.es
medicina
universitaria
AND "DR. JOSÉ ELEUTERIO GONZÁLEZ"
EDITORIAL COMMITTEE
General Director
Chief editor
Editor
Editor
Santos Guzmán López
Ariel Ernesto Arias Ramírez
Félix Ramón Cedillo Salazar
Alejandro Arroliga
David Gómez Almaguer
Norbert W. Brattig
Francisco Javier Bosques Padilla
María de los Ángeles Castro Corona
Ottawa, Canadá
Temple, EEUU
Hamburgo, Alemania
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
DF, México
Francisco Forriol Campos
Madrid, España
Alejandra García Quintanilla
Mérida, México
Elvira Garza González
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
DF, México
David Kershenobich Stalnikowitz
DF, México
Francisco López Jiménez
Rochester, EEUU
Xavier López Karpovitch
DF, México
Laura E. Martínez de Villarreal
Nahum Méndez Sánchez
Monterrey, México
Nueva York, EEUU
Mario Henry Rodríguez
Cuernavaca, México
Puebla, México
Guillermo J. Ruiz Delgado
Puebla, México
José Javier Sánchez
Madrid, España
Josep María Segur Vilalta
Gregorio A. Sicard
Antonio Costilla Esquivel
Monterrey, México
Rolando Tijerina Menchaca
Lyuba Varticovski
Juan Pablo Figueroa Delgado
Monterrey, México
Alejandro Ruiz Argüelles
Monterrey, México
Emma Bertha García Quintanilla
DF, México
Guillermo I. Pérez Pérez
Eloy Cárdenas Estrada
English translation and style:
Monterrey, México
Claudia Elizalde Molina
Isaías Rodríguez Balderrama
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 62, enero-marzo 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.
Reservados todos los derechos. El contenido de la presente publicación no puede ser reproducido, ni transmitido por ningún procedimiento electrónico o mecánico, incluyendo
fotocopia, grabación magnética, ni registrado por ningún sistema de recuperación de información, en ninguna forma, ni por ningún medio, sin la previa autorización por escrito del
titular de los derechos de explotación de la misma. Cualquier forma de reproducción, distribución, comunicación pública o transformación de esta obra sólo puede ser realizada
con la autorización de sus titulares, salvo excepción prevista por la ley. Impresa por Editorial de Impresos y Revistas S. A. de C. V. Emilio Carranza No. 100 Col. Zacahuizco C.P. 03550.
Delegación Benito Juárez, México D.F. Este número se terminó de imprimir en marzo 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.
medicina
universitaria
AND “DR. JOSÉ ELEUTERIO GONZÁLEZ”
Contents
EDITORIAL
Volume 16
Issue 62
January-March 2014
1 One big evolutionary step
S. Guzmán-López, F. R. Cedillo-Salazar, D. Gómez-Almaguer and F.J.
Bosques-Padilla
ORIGINAL ARTICLES
2 Discrimination in clinical settings and its relationship to depression and anger
in women living with HIV
J. Moral-de la Rubia and M. P. Segovia-Chávez
9 Frequency of metabolic syndrome in women treated at the Menopause Clinic
of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico
M. Cervantes-Flores, J. Vázquez-Méndez, D. Saldívar-Rodríguez, O. VidalGutiérrez, I. Y. González-Carrillo and G. Guerrero-González
12 Correlation between BMI and climateric symptoms in menopausal women
I. Y. González-Carrillo, J. Vázquez-Méndez, G. Guerrero-González, O. Vidal-Gutiérrez and M. Cervantes-Flores
15 Infiltration vs. instillation of ropivacaine 7.5% in radical mastectomies for
postoperative analgesia
B. I. Yolanda-Prieto, A. L. Millán-Corrales, D. Palacios-Ríos, B. I. GarduñoChávez, N. G. López-Cabrera, G. A. Millán-Cornejo and B. T. González-Rocha
19 Maternal mortality and severe obstetric morbidity in a tertiary care hospital
J. L. Iglesias-Benavides, M. S. Vidales-Hernández, W. E. Treviño-Ledezma, S. N.
Delgado-Muñiz and A. Guzmán-López
scientific LETTER
25 Sweet syndrome presenting late after non Hodgkin’s lymphoma and dermatomyositis
L. A. Olguín-Ramírez, J. C. Jaime-Pérez, C. Mendoza-Rodríguez and D. GómezAlmaguer
REVIEW ARTICLES
28 Mild cognitive impairment
J. Isordia-Martínez, F. Gongora-Rivera, H. Leal-Bailey and X. Ortiz-Jiménez
37 Trichosporon spp.: an emerging fungal pathogen
A. M. Montoya and G. M. González
Medicina Universitaria 2014;16(62):1
medicina
universitaria
www.elsevier.com.mx
Editorial
One big evolutionary step
It’s been a long and exciting journey since it was decided
that a medical journal should be a fundamental part of the
strategy to fulfill our Institution’s Subdivision of Continuing
Medical Education’s main goal, which is to strengthen the
bond between graduated biomedical professionals and our
medical school, keeping them on the leading edge of medical knowledge. And so, the Medicina Universitaria journal
was born.
As the years went by, an evident evolution occurred in
this journal. Since the first issue was published in January
1970, a constant transformation has taken place. We now
have a larger group of people involved in its process, a new
and renovated image, improved economic support, and a
well-established trimestral periodical production. Furthermore, a greater number of papers are considered for publication, and last but not least, we are now published by
Elsevier, a very well-known and prestigious editorial company.
Today, we are very proud to announce that another important evolutionary change in our journal has occurred. From
now on, the entire Medicina Universitaria journal will be
published in the English language, starting with this year’s
first issue. Although it could be seen as a small transformation, in reality it is a very big one. This will allow our journal
to be read by almost all health professionals worldwide, as
English is the world’s official scientific language. Thus, the
possibility of our articles being read and cited is far greater;
the scientific medical community from larger countries such
as India, China, Brazil, Russia etc., will have the possibility
to read and discuss our papers. Hopefully, this will keep us
in the right direction to become an indexed medical journal, as we have been so far.
In spite of these transformations, we are completely certain
that something very important in our journal has not changed; it’s still being made by a selfless group of professors
who follow the original vision of it is founder Dr. Álvaro Gómez-Leal. That is, to be an effective journal that assists
health professionals in their continuous pursuit of excellence and in giving their patients the best medical treatment
available in a humanist way. This is the engine that moves
every physician’s mind; to reach their main practice’s objective by offering the best medical treatment possible, in
accordance with international guidelines, in a human, caring, and passionate way.
Throughout the last four decades, our journal has played
an important role as a communication tool. Its pages have
witnessed some of the most relevant, dramatic and visionary advances in the health sciences over the last 44 years.
That being said, we are sure that one of Dr. Gómez-Leal’s
greatest legacies was his original idea to create a useful
journal within our medical school, to serve all generations
of health professionals.
We wish to congratulate everyone who has participated in
any way to make our Medicina Universitaria journal a reality. We are proud to present it in its new format which will
help everybody in his or her constant pursuit of excellence
and truth. Let’s enjoy it.
S. Guzmán-López, MD
General Director
F. R. Cedillo-Salazar, MD*
Chief Editor
D. Gómez-Almaguer, MD
Editor
F. J. Bosques-Padilla, MD
Editor
* Corresponding author: Eduardo Aguirre Pequeño Avenue and Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico.
Telephone: +52 (81) 8329 4193, 8346 1370, 8347 5867. Fax: 8333 6687. E-mail address: [email protected] (F. R. Cedillo-Salazar).
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados.
Medicina Universitaria 2014;16(62):2-8
medicina
universitaria
www.elsevier.com.mx
Original article
Discrimination in clinical settings and its relationship to depression
and anger in women living with HIV
J. Moral-de la Rubia*, M. P. Segovia-Chávez
Faculty of Psychology, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: November 2012; Accepted: November 2013
KEYWORDS
Depression; Anger;
Discrimination;
Women; AIDS; Mexico.
Abstract
Objectives: To describe the frequency of feared discrimination in various social situations and of
perceived discrimination in clinical settings, as well as to study the relationship between discrimination and depression and anger in women living with human immunodeficiency virus (HIV).
Material and methods: The scale of Feared and Perceived Discrimination for Women with HIV
(DTP-40-MV), the Beck Depression Inventory (BDI-2), and the Anger Expression scale of StateTrait-Anger Expression Inventory (STAXI-2-AX/EX) were applied to a random sample of 200 women living with HIV.
Results: These women feared being discriminated against, perceived discrimination upon the
review of medical records, but perceived little discrimination in clinical care. A model with
good adjustment to the data showed that the fear of being discriminated against creates a disposition toward perception of discrimination in the clinical settings (latent variable with 2 indicators: review of the medical records and clinical care) and increases cognitive/affective depressive symptoms; higher anger control decreases the anger manifestation; greater
discrimination perceived in the clinical settings decreases anger control, which facilitates the
expression of anger and slows cognitive/affective depressive symptoms; and these latter symptoms sensitize the perception of discrimination before the clinical records.
Conclusion: Feared discrimination is a clinically relevant aspect due to its frequency and effect
on depressive symptoms and perception of discrimination before the review of medical records.
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos
los derechos reservados.
Introduction
Human immunodeficiency virus (HIV) infection is a chronic
degenerative disease which has a life expectancy of over 40
years if detected early, and with an uninterrupted adherence to an antiretroviral treatment under medical supervision.
Nowadays, HIV infection eventually evolves into a very advanced immunodeficiency stage, in which the organism
* Corresponding author: Dr. Carlos Canseco 110, Mitras Centro, Z.P. 64460, Monterrey, N. L., México. Telephono: (81) 8333 8233, ext. 423.
Fax: ext. 103. E-mail address: [email protected] (J. Moral-de la Rubia).
Discrimination in clinical settings and its relationship to depression and anger in women living with HIV
undergoes other diseases as a result of the body’s low immunological competence such as Pneumocystis jiroveci
pneumonia or Kaposi’s sarcoma.1 When first diagnosed as
HIV-seropositive, the patient is faced with a death prognosis, as well as a lifetime of expensive treatments with side
effects. Additionally, there is the social stigma involved with
the diagnosis. HIV infection diagnosis is associated with morally-condemned behaviours such as men having sex with
men, having multiple and concurrent sex partners, commercial sex, and intravenous drug use.2
In recent years, HIV infection risk factors have shifted,
gaining ground amongst heterosexual transmission.3 In 2013,
females represented half of the cases worldwide (17.7 million out of the 35.3 million infected people are women); as
known, in the past the epidemic was found predominantly
in males.4 In Mexico, the ratio of female cases has increased
since 1983; however, cases are still mostly found in males.3
From 1983 to 2012, 18% of the cases corresponded to
women and 82% to men.5 In 2013, in Nuevo Leon, Mexico
the number of HIV-seropositive people was 4,938 with a
male:female ratio of 7 to 1.5
Discrimination and stigmatization against people living
with HIV and those around them is one of this infectious diseases’ negative consequences, and a major obstacle in prevention and assistance.6 Oftentimes people with HIV are
ostracized by their families as well as their communities;7
they are subjected to social and institutional discrimination, and on occasion even denied access to healthcare, insurance coverage, entry to some countries, and access to
job opportunities.8 Fear of discrimination makes people
avoid detection tests, which impedes early treatment.9
Depression is twice as common in people with HIV compared to the general population.10 Discrimination contributes
to depression, especially in women.11 We must point out
that most people experience anger when discriminated against as they feel their rights are being infringed upon. If
discrimination persists and intensifies, it usually leads to
helplessness and depression; however, there are people who
do not react with anger but go straight to depression due
to a personal history of helplessness.12
Anger, especially uncontrolled anger, can have a negative
effect in medical attention as well as in the provider-patient relationship, possibly acting as a cause of discrimination. On the other hand, its assertive expression can
increase awareness and a possible rectification of the injustice suffered.13 It is exactly this complaint of discrimination
from HIV seropositive patients which is the most frequent in
the clinical field, in which there is a great sensitivity to the
patients’ rigths.14
Even though there are studies that consider depression
and anger as a response to discrimination against HIVseropositive patients,15,16 these studies do not distinguish
between discrimination feared (expectations) and discrimination perceived (experienced); besides, all of these studies have been conducted outside of Mexico. Therefore, the
objective of the present investigation is to describe the frequency of feared discrimination in different social situations, and perceived discrimination in clinical settings
against HIV-seropositive women, as well as to study the relationship between discrimination, depression, and anger in
women living with HIV, in which anger and depression are
consequences of discrimination.11,12,15,16 Anger management
3
increases depressive symptoms, and the manifestation of
anger decreases them.13,17
Methods and materials
The population of our study consisted of women diagnosed
as HIV-positive getting medical attention in Nuevo Leon.
The inclusion criteria were: being 18 years or older, knowing
how to read and write, and signing a consent form before 2
witnesses.18 Exclusion criteria were the presence of symptoms impeding a proper comprehension and focus on the
questionnaire.
We took into consideration the recommendations made by
the American Psychological Association for conducting research with human participants,19 thus we provided each
participant with information on the purpose of the study, guaranteed confidentiality of their information, and requested a signed consent form.
Considering that 60% of a population of 576 cases of women with HIV reported in Nuevo Leon during 20095 suffered
discrimination,20 with a 95% confidence interval and a 5%
exact standard error, we required a sample of 200 individuals. The 200 women who participated in the study were
outpatients in Monterrey. They were interviewed by a psychologist while waiting for their appointments. The sampling process was performed between June 2010 and May
2011.
In a face-to-face interview we questioned patients in order to obtain sociodemographic and clinical information.
After the interview, the patients were given 3 scales so they
could answer them in the presence of the interviewer.
The scale of feared and perceived discrimination for
women with HIV (DTP-40-MV)21 was developed for this study
at a qualitative phase.19 This scale measures discrimination
in expectation and perception aspects as a consequence of
being HIV positive or having acquired immunodeficiency
syndrome (AIDS). It consists of 40 Likert scale questions with
a range from 1 “nothing” to 5 “completely”. Patients are
presented with a series of situations of discrimination
against HIV-seropositive people and/or people with AIDS,
and asked how much these situations describe their own expectations or experiences. All items are direct and their total discrimination score is obtained simply by adding them.
Their internal consistency is high (α = 0.92). It incorporates
6 correlated factors: feared discrimination with 11 indicators (α = 0.94), perceived discrimination at work and in the
neighborhood with 8 indicators (α = 0.93), perceived discrimination at home with 8 indicators (α = 0.88), perceived
discrimination in clinical care with 5 indicators (α = 0.91),
perceived discrimination upon review of medical records
with 2 indicators (α = 0.91), and moments of discrimination with 6 indicators (α = 0.85), with an accepted scalefree least squares: χ2/gl = 1.75, GFI = 0.94, AGFI = 0.93, NFI
= 0.92, RFI = 0.91, and RMS SR = 0.01.21 These psychometric
properties were estimated in the same sample as the study.
The BDI-222,23 consists of 21 questions with 4 options each
scored 0 to 3. A higher score reflects a greater presence and
intensity of depressive symptoms. The adjustment of the
model of 2 correlated factors by least squares was acceptable: χ2/gl = 2.14, FD =2.02, PNCP = 1.08, GFI = 0.81, AGFI =
0.76, and RMSEA = 0.08.
4
The Anger Expression Scale of State-Trait-Anger Expression Inventory (STAXI-2-AX/EX)24,25 includes 21 Likert scale
questions ranging from 1 “almost never” to 4 “almost always”. It uses a 4-point frequency scale, 3 with 6 items
each (anger control-out, anger control-in, anger expressionout), and 1 with 3 items (anger expression-in). The total
score is obtained by adding the items. Total score of anger
expression is obtained by adding the 9 items of anger expression-out and anger expression-in, constant 39 and deducting 12 items in anger control-in and anger control-out.
In the present sample, in order to accomplish an acceptable
solution in the confirmatory factor analysis, following the
exploratory factor result, we added anger expression-in and
anger expression-out (α = 0.89), anger control-in remained
with 6 items (α = 0.88), just as anger control-out (α = 0.79).
This correlated-factors model displayed good adjustment to
generalized least squares: χ2/gl = 2.04, FD = 1.54, PNCP =
0.79, GFI = 0.84, AGFI = 0.80, and RMSEA = 0.07. The internal consistency of the 21 items was high (α = 0.89).
Using statistics we analyzed the relationship between
sociodemographic and affective variables with 3 subscales
of studied discrimination through Pearson’s product-moment correlation coefficient (with numerical variables),
biserial-punctual (with dichotomous variables), and ETA
(with polytomous variables). We compared the statistical
averages of each of the 3 studied discrimination subscales;
analysis of variance and Student t test were used for
paired samples.
Using linear structural equation modelling, we contrasted a relationship model between discrimination, depression, and anger. We performed this utilizing the maximum likelihood method.
For linear structural equation modeling, a model was
contrasted between discrimination, depression, and anger
using the maximum verisimilitude method.This method
was chosen because it is the most accurate for parameter
estimation and the multivariate normality assumption, required for this method, was fulfilled as it was indicated by
a normalized value of the multivariate kurtosis of Mardia
(critical reason) lower than 2.26 Nine adjustment indexes
were considered: the statistical chi-squared (x2), the quotient between the statistical chi-squared and its degrees
of freedom (x2/gl), the function of discrepancy (FD), the
parameter of non-central populations (PNCP), Jöreskog
and Sörbom’s goodness-of-fit index (GFI) and its corrected
form (AGFI), Bentler-Bonett’s normed fit index (NFI)
and comparative fit index (CFI), and Steiger-Lind’s root
mean square error of approximation (RMSEA). The following were stipulated as good adjustment values: p of χ2
> 0.05, χ2/gl ≤ 2, FD and PNCP ≤ 1/5 of the corresponding
values to the independent model, GFI and CFI ≥ 0.95, AGFI,
NFI and RFI ≥ 0.90, RMSEA and RMS SR ≤ 0.05. And as aceptable adjustment values: p of χ2 > 0.01 χ2/gl ≤ 3, FD and
PNCP ≤ 1/4 of the values corresponding to the independent
model, GFI, CFI and RFI ≥ 0.85, AGFI and NFI ≥ 0.80, RMSEA
and RMS SR < 0.08. 26,27 The correlation values less than
0.30 were considered low, from 0.30 to 0.69 were considered moderate, and greater than 0.69 were considered
high. 28 In contrasts of parameters, the equivalence to 0
null hypothesis was rejected with p ≤ 0.05.28
Results
Sample description
Seventy-nine percent of patients reported having been infected by their spouse or live-in partner, 15.5% by a casual
partner, 2% by a customer, 1.5% by a partner outside of marriage, 1% by a boyfriend, 0.5% as a result of rape, and 0.5%
by vertical transmission (mother-child). The average time
elapsed from the moment they had been diagnosed was 3.7
years (SD= 3.17), varying from 1 month to 18 years. Patients’
average age was 34.8 years (SD = 8.63; 18 to 50 years). Median and average level of education was incomplete junior
high school. Forty-three percent of participants reported
being married, 22.5% single, 14% living with a partner, 9.5%
widows, 6% separated, and 5% divorced. Sixty-two percent
of these women reported having children. Concerning religious beliefs; 88.5% were catholic and 11.5% christian.
Discrimination feared in diverse social
situations
By dividing the average discrimination feared subscale (M =
35.2) by its number of items (11), and rounding up the result, we obtained 3 which corresponded to “a lot”, in a range from 1 (“nothing”) to 5 (“completely”).
Feared discrimination correlated with a younger age in the
participants, a lower average of their children’s ages, a lower
frequency in attendance to religious services, their marital
status, religion, and occupation; moreover, and among the
affective variables with a higher total score of anger, higher
anger expression-out, and lower anger control-out. Single
women who were living from commercial sex and catholics
had a greater fear of being discriminated against (Table 1).
Discrimination perceived in clinical care, and
upon review of medical records
After dividing the average of the discrimination perceived
subscale in the clinical care (M = 11.0) by the number of
items (5) and rounding up the result, we obtained 2, which
corresponds to “a little”.
Discrimination perceived in clinical care was independent
of sociodemographic variables. It correlated with a lower
total score of depression and its 2 factors of cognitive-affective and somatic-motivational symptoms, as well as a
higher total score of anger, higher anger expression-out,
and a lower anger control-out (Table 1).
After dividing the average of the discrimination perceived
upon review of medical records (M = 6.4) by the number of
items (2) and rounding up the result, we obtained 3, which
corresponds to “a lot”.
Discrimination perceived upon review of medical records correlated with religion (catholics perceived more discrimination),
a higher total score of anger, lower anger control-out, and a
lower frequency of attendance to religious services (Table 1).
Correlation and differences of averages
between 3 discrimination subscales
Correlation of feared discrimination with perceived discrimination in clinical care was moderate (r = 0.40, p < 0.01),
5
Table 1 Discrimination correlations with emotional and sociodemographic variables.
Discrimination
Emotional and sociodemographic
Variables
Feared
PAC
PEC
Total score
0.06 ns
-0.25**
0.04 ns
Cognitive-affective(1)
0.08 ns
-0.27**
0.03 ns
0.01 ns
-0.15*
0.05 ns
Total score
0.22**
0.30**
0.20**
Expression-out(1)
0.20**
0.28**
0.13 ns
Control-in(1)
-0.05 ns
-0.12 ns
-0.14*
Control-out(1)
-0.25**
-0.25**
-0.20**
Age(1)
-0.18**
-0.09 ns
-0.07 ns
Number of children(1)
-0.12 ns
-0.11 ns
-0.01 ns
(1)
Depression
(BDI-21)
Somatic-motivational
(1)
(1)
Anger
(AX-21)
-0.20**
-0.04 ns
-0.09 ns
Level of education(1)
-0.04 ns
-0.01 ns
0.03 ns
Religious practices
-0.31**
-0.12 ns
-0.17*
-0.20**
-0.13 ns
-0.22**
Marital status(3)
0.45**
0.22 ns
0.21 ns
Occupation
0.30**
0.19 ns
0.09 ns
Children’s average age
Sociodemographic
variables
(1)
(1)
Religion(2)
(3)
(1)
r = Pearson’s product-moment, (2) rbp: biserial-punctual and (3) η = eta.
* p ≤ 0.05 ns p > 0.05. ** p ≤ 0.01.
PAC: discrimination perceived in clinical care; PEC: discrimination perceived upon review of medical records. Religion: (1) = catholic,
(2) = christian.
whereas correlation with perceived discrimination upon
review of medical records was low (r = 0.29, p < 0.01). Correlation between both perception subscales was moderate
as well (r = 0.40, p < 0.01).
In order to accomplish a homogeneous range from 1 to 5,
thus to be able to make intra-group average comparisons,
we divided each scale’s score by its number of items. There
was a difference between averages in the 3 subscales (F[2,
398] = 68.76, p < 0.01, assuming sphericity in the Mauchsly
test: W = 0.99, χ2[2, N = 200] = 1.11, p = 0.57). The average
of perceived discrimination in clinical care was lower than
the average of perceived discrimination upon review of medical records (t[199] = -10.67, p < 0.01), and feared discrimination average (t[199] = -9.92, p < 0.01), being the
averages statistically equivalent in these last 2 subscales
(t[199] = -0.20, p = 0.83) (Fig. 1).
Structural model of discrimination, anger, and
depression
The model was calculated only with the subscales. We specified a latent perception of discrimination in clinical settings factored with 2 indicators (clinical care and upon
review of medical records). Given its highest correlation with the 3 discrimination subscales, we considered cognitive-motivational depression symptoms as well as anger
expression-out and control-out.
Cognitive-affective symptoms correlated with anger expression-out (r = -0.19, p < 0.01) and were independent
from anger control (r = 0.13, p = 0.06).
Taking into account these last 2 correlations, we specified
a first model where the loss of anger control-out predicted
anger expression-out. Anger expression-out predicted a reduction of the cognitive-affective symptoms of depression.
Feared discrimination (manifest exogenous variable) predicted awareness of perceived discrimination in clinical settings (latent endogenous variable), loss of anger control-out,
anger expression-out, and cognitive-affective symptoms of
depression. Perceived discrimination in clinical settings predicted loss of anger control-out, anger expression-out, and
a decrease in cognitive-affective symptoms of depression.
Three out of the 9 adjustment indexes were bad (χ2[4, N =
200] = 20.49, p < 0.01, χ2/gl = 5.12 and RMSEA = 0.14), 2
were acceptable (AGFI = 0.84 and CFI = 0.91), and 4 good
(GFI = 0.97, NFI = 0.90, FD = 0.10 and PNCP = 0.08). Three
parameters of the directional relations of the structural
model were not significant: the determination of anger control-out and anger manifestation due to feared discrimination, and the determination of the cognitive-affective
symptoms due to expression-out. We explained 28% of
perceived discrimination in clinical settings, 14% of anger
control-out, 30% of anger expression-out, and 14% of cognitive-affective symptoms of depression (Fig. 2).
According to the BDI in samples from the United States22
and Spain23, the internal consistency of its 21 items of BDI-2
was high, varying from 0.87 to 0.92; BDI-2’s factorial analysis provided a 2 correlated factors solution (cognitive-affective and somatic-motivational symptoms) with an acceptable
adjustment to data. In the present Mexican sample, BDI-2’s
6
Medidas en un rango de 1 a 5
χ2 (4, N = 200) = 20.49, p < 0.01, χ2/gl = 5.12,
GFI = 0.97, AGFI = 0.84, CFI = 0.91, NFI = 0.90,
FD = 0.10, PNCP = 0.08 y RMSEA = 0.14
3.25
3.22
3.20
3.00
14%
2.75
-0.08
Anger
control-out
e1
2.50
Discrimination
feared
-0.33
2.20
2.25
DT
PAC
-0.46
PEC
DT: discrimination feared; PAC: discrimination perceived in
clinical care; PEC: discrimination perceived upon review of
medical records.
30%
e2
0.53
-0.01
Anger
expression-out
0.29
-0.16
e3
Cognitive-affective
depression
factor
Discrimination
perceived
in clinical settings
e6
0.68
0.58
14%
-0.34
Figure 1 Averages diagram.
28%
0.18
Review of
medical
records
Clinical
care
34%
21 items had high internal consistency (α = 0.94), as well as the
14 items of factors of cognitive-affective symptoms (α = 0.93)
and the 7 factors of somatic-motivational symptoms (α = 0.83).
After reviewing the adjustment improvement indexes of
this first model, we suggested the introduction of determination of perceived discrimination upon review of medical
records by cognitive-affective symptoms of depression. We
must take into account that when we partialized the effect
of discrimination perceived upon review of medical records
(latent factor), the correlation between anger expressionout and cognitive-affective symptoms of depression ceased
to be significant (rp = -0.12, p = 0.08). When we partialized
the effect of discrimination perceived in clinical care and
upon review of medical records (latent factor), the correlation between discrimination feared and anger expressionout ceased to be significant (r p = 0.13, p = 0.07). The
correlation between perceived discrimination and anger control-out only ceased to be significant when we partialized anger expression-out apart from the latent factor
(rp = -0.12, p = 0.09). On the contrary, the correlation of
feared discrimination and cognitive-affective symptoms of
depression was significant, when we partialized anger expression-out effect and anger control-out (rp = 0.15, p <
0.05), and when partializing the effect of perceived discrimination in clinical care (rp = 0.17, p = 0.01), yet it had not
been before (r = 0.08, p = 0.27). Furthermore, when we
patialized the effect of perceived discrimination in clinical
care, the correlation between cognitive-affective symptoms
of depression and perceived discrimination upon review of
medical records was significant (rp = 0.16, p < 0.05), yet it
had not been before (r = 0.03, p = 0.68).
We specified a second model, eliminating non-significant
parameters from the first one and considering partial correlations data, as well as suggested correction from the adjustment improvement indexes. Loss of anger control-out
predicted anger expression-out. Feared discrimination (exogenous manifest variable) predicted perceived discrimination in the clinical setting (endogenous manifest variable)
and cognitive-affective symptoms of depression. Perceived
discrimination in the clinical setting predicted anger control-out and anger expression-out, as well as cognitiveaffective symptoms of depression. Cognitive-affective symptoms predicted perception of discrimination upon
review of medical records.
e4
46%
e5
Figure 2 Standardized model of anger and depression as a
consequence of discrimination, estimated by maximum verisimilitude.
The value of the 9 adjustment indexes was good. The parameters of the 6 directional relationships in the structural
model, and both of the parameters in the measurement model were significant. We explained 25% of perceived discrimination in the clinical setting, 17% anger control-out, 31%
anger expression-out, and 33% cognitive-affective symptoms of depression (Fig. 3).
Discussion
These HIV-seropositive women, mostly young women, reported fearing being discriminated against in several social situations and perceive discrimination upon review of medical
records; however, the perception of discrimination in clinical care, without considering review of medical records,
was low. We must point out that perception of discrimination upon review of medical records, within the group of the
6 subscales of DTP-40-MV, defined a factor of second order
with feared discrimination, thus reflecting a greater connotation of expectations rather than facts. Therefore, this
perception seems to be generated by administrative and auxiliary staff, and not at the moment of going in to see the
doctors, nurses, psychologists, and social workers. If any of
the previous studies in Mexico have directed discrimination
perception in the clinical setting,29 these also seem to focus
upon review of medical records amongst administration
staff and auxiliaries.
Moreover, we must point out the fact that the low frequency of discrimination in clinical consultations observed
is coherent with other reports.30 This tendency is also reflected by the second National Survey on Discrimination in
Mexico,31 in which as compared with the first one,32 the percentage of people who would not agree to live with an HIVseropositive person went from 44% to 35.9%.
Besides the fact that the expected discrimination level in
different social situations was higher than the discrimination perception in clinical care, requiring intervention, such
χ2 (6, N = 200) = 6.21, p = 0.40, χ2/gl = 1.03,
GFI = 0.99, AGFI = 0.96, CFI = 1, NFI = 0.97,
FD = 0.03, PNCP < 0.01 y RMSEA = 0.01
17%
e1
Anger
control-out
Discrimination
feared
-0.41
-0.44
0.50
31%
e2
25%
Anger
expression-out
0.20
0.40
Discrimination
perceived
in clinical settings
e6
0.64
0.74
33%
-0.65
e3
Cognitive-affective
factor
of depression
Review of
medical
records
0.36
Clinical
care
44%
e4
41%
e5
Figure 3 Reviewed standardized model of anger and depression as a consequence of discrimination, estimated by maximum verisimilitude.
expectations influence perception, creating awareness. This
is an aspect that is not addressed in any program directed
toward HIV-seropositive patients.33,34
Frequency of attendance to religious services is an indicator of a degree of religiousness, in addition to a strong social support. This study’s correlated data show that women
who practice their religion more often suffer less expectations of being rejected, and perceive less discrimination
upon review of medical records, as observed in other researches.35 We shall not attribute this to the context of religious community communication and support, since their
effect is often the opposite, 36 this due to the fact that
amongst women who practice their religion more often are
the widows and married who were infected by their husbands, which frees them from the social stigma of the main
risk factors of HIV infection, and brings compassion from the
people closer to them; on the contrary, amongst women
who practice religion the least there are single women and
sex-workers who attract greater social stigma.12,20 In favor
of this argument we have the correlations between religious
practice and discrimination increased when calculated
without married women, but it ceases to be significant
when single women are disregarded, making the association
between marital status and religious practice significant (η
= 0.38, p < 0.01).
Within depression, the cognitive-affective symptoms factor was the most related to discrimination, which can be
explained by a higher affinity to evaluated contents in comparison to the somatic-motivational symptoms factor. Contrary to what was expected, cognitive-affective symptoms
of depression seem to be independent of feared discrimination, but when we partialized the effect of anger controlout and anger expression-out, the relation was significant;
that is, anger would disguise the relationship with the adjustment improvement of data that fear of being discriminated against increases cognitive-affective symptoms of
depression.
7
Furthermore, perception of discrimination in the clinical
setting which generated an activating reaction (more anger
and less depression) was hiding the fact that the cognitiveaffective symptoms of depression aroused by feared discrimination increased the perception of discrimination upon
review of medical records.
These data seem to reflect the fact that these women
consider it a right to be attended to and an obligation of
clinical and administrative staff to provide respectful and
quality care,31 hence the infringement of this right creating
a reaction of anger which even reduces depressive feelings
or thoughts. This relation is so well defined that it annuls
anger expression-out over depression, when there is a negative correlation between these 2 variables.
We must point out as one of the limitations of the study
the fact that we utilized a sample composed solely of women. Given the size of the sample, with a sample fraction of
a third of the women attended to in Nuevo León, Mexico,
this sample is representative, with an absolute error of 5%
and a confidence interval of 95%; however, the extrapolation to similar populations must be made in the form of a
hypothesis.
In conclusion, these HIV-seropositive women fear being
discriminated against; however, the perception of discrimination in clinical care, aside from review of medical records, is low. As is the perception of a clinical chart with a
different color from other patients’, or subtle markings,
certain gestures or distances from administrative and auxiliary staff seem to generate expectation of discrimination
which is not confirmed by the doctors.
The expectation of discrimination increases depressive
thoughts and feelings, as expected; however, this relation is
only observed when we statistically control the effect of
perception of discrimination in clinical care by a strong anger outburst (activator) which it generates; besides, the expectation of discrimination sensitizes perception of
discrimination, in accordance with expectations.
On the other hand, cognitive-affective symptoms of depression aroused by the expectation of discrimination sensitize perception of discrimination upon review of medical
records, which seems to define a closed self-reinforcing circle. This is broken by an anger outburst when discrimination
in the clinical settings by doctors is perceived, when patients feel deprived of care which they are entitled to, and
which has to be performed then and there without complaining.
Based on these data, we suggest contemplating the expectation of discrimination in interventions within this population of women with HIV, especially because of its
depressive effect and sensitizing to the perception of discrimination upon review of medical records by administrative
and auxiliary staff, which constitutes as the most frequent
act of perceived discrimination in the clinical setting, even
when in the consult with doctors, nurses, psychologists, and
social workers they do not confirm the expectation generated by this first impression.
Conflicts of interest
The authors have no conflicts of interest to declare.
8
Funding
No financial support was provided.
References
1. Nakagawa F, Lodwick RK, Smith CJ, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS
2012;26:335–343.
2. Flores PF, Leyva FR. Representación social del SIDA en estudiantes de la Ciudad de México. Salud Publica Mex 2003;45(suppl
5):624-631.
3. Magis C, Barrientos H. VIH/SIDA y salud pública. Manual para
personal de salud (2ª. edición). Cuernavaca, Morelos, México:
Instituto Nacional de Salud Pública (INSP); 2009.
4. Joint United Nations Programme on HIV/AIDS (UNAIDS). Global
report. UNAIDS report on the global AIDS epidemic 2013. Ginebra: WHO Library Cataloguing-in-Publication Data; 2013.
5. Centro Nacional para la Prevención y el Control del VIH/SIDA
(CENSIDA). Vigilancia epidemiológica de casos de VIH/SIDA en
México. Registro nacional de casos de SIDA. Actualización al 30
de junio de 2013. México, DF: CENSIDA; 2011.
6. Lee RS, Kochman A, Sikkema KJ. Internalized stigma among
people living with HIV/AIDS. AIDS Behav 2002;6:309-319.
7. Dray-Spira R, Legeai C, Le Den M, et al. Burden of HIV disease
and comorbidities on the chances of maintaining employment
in the era of sustained combined antiretoviral therapies use.
AIDS 2012;26:207-215.
8. Maman S, Abler L, Parker L, et al. A comparison of HIV stigma
and discrimination in 5 international sites: The influence of
care and treatment resources in high prevalence settings. Soc
Sci Med 2009;68:2271-2278.
9. Hosseinzadeh H, Hossain SZ. Functional analysis of HIV/AIDS
stigma: consensus or divergence? Health Educ Behav
2011;38:584-595.
10. Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J
Psychiatry 2001;158:725-730.
11. Li L, Lee SJ, Thammawijaya P, et al. Stigma, social support, and
depression among people living with HIV in Thailand. AIDS Care
2009;21:1007-1013.
12. Zukoski AP, Thorburn S. Experiences of stigma and discrimination among adults living with HIV in a low HIV-prevalence context: A qualitative analysis. AIDS Patient Care STDS
2009;23:267-276.
13. Hansen N, Sassenberg K. Exploring the self-directed anger of
the stigmatized: The interplay between perceived legitimacy
and social identification. Group Processes Intergroup Relations
2011;14:807-818.
14. Health Policy Initiative (HPI). Measuring the degree of HIV-related stigma and discrimination in health facilities and providers:
Working report. Washington, DC: HPI; 2010.
15. Vanable PA, Carey MP, Blair DC, et al. Impact of HIV-related
stigma on health behaviors and psychological adjustment
among HIV-positive men and women. AIDS Behav 2006;10:473482.
16. Bogart LM, Cowgill BO, Kennedy D, et al. HIV-related stigma
among people with HIV and their families: A qualitative analysis. AIDS Behav 2008;12:244-254.
17. Borders A, Liang CT. Rumination partially mediates the associations between perceived ethnic discrimination, emotional distress, and aggression. Cultur Divers Ethnic Minor Psychol
2011;17:125-133.
18. Secretaría de Salud. Norma Oficial Mexicana NOM-039SSA2-2002. Para la prevención y control de las infecciones de
transmisión sexual. México: Diario Oficial de la Federación,
2003, 19 de septiembre: 100-117. Disponible en: http://www.
hsph.harvard.edu/population/aids/mexico.aids.02.htm
19. American Psychological Association. Ethical principles of
psychologists and code of conduct. American Psychologist
2002;57:1060-1073.
20. Moral J, Segovia MP. Discriminación en mujeres que viven con
VIH/SIDA. Revista Iberoamericana de Psicología y Salud
2011;2:139-159.
21. Moral J, Segovia MP. Propiedades psicométricas de la escala
de discriminación temida y percibida para mujeres con VIH
(DTP-40-MV). Revista Iberoamericana de Psicología y Salud
2013;4:37-62.
22. Beck AT, Steer RA, Brown GK. Manual for the Beck Depression
Inventory-II.San Antonio, TX: Psychological Corporation; 1996.
23. Sanz J, Perdigón LA, Vázquez C. Adaptación española del Inventario para la Depresión de Beck-II (BDI-II): 2. Propiedades psicométricas en población general. Clínica y Salud 2003;14:249280.
24. Spielberger CD. State-Trait Anger Expression Inventory-2
(STAXI-2). Professional manual. Florida: Psychological Assessment Resources; 1999.
25. Moral de la Rubia J, González Ramírez MT, Landero Hernández
R. Factor structure of the STAXI-2-AX and its relationship to the
burnout in housewives. Span J Psychol 2010;13:418-430.
26. Kline RB. Principles and practice of structural equation modeling (3rd ed.). New York: The Guilford Press; 2010.
27. Moral J. Análisis factorial confirmatorio. En: Landero R, González MT (eds.), Estadística con SPSS y metodología de la investigación. México, DF: Trillas; 2006. p. 445-528.
28. Cohen J, Cohen P, West SG, et al. Applied multiple regression/
correlation analysis for the behavioral sciences (3rd ed.). Mahwah, NJ: Psychology Press; 2003.
29. Infante C, Zarco A, Magali S, et al. El estigma asociado al VIH/
SIDA: el caso de los prestadores de servicios de salud en México. Salud Pública Méx 2006;48:141-150.
30. Córdova JA, Ponce-de-León S, Valdespino JL. 25 años de SIDA
en México. Retos, logros y desaciertos. México: CENSIDA; 2009.
31. Consejo Nacional para Prevenir la Discriminación (CONAPRED).
Encuesta Nacional sobre Discriminación en México 2010. Resultados generales. México, DF: CONAPRED; 2011.
32. Consejo Nacional para Prevenir la Discriminación (CONAPRED).
Primera encuesta nacional sobre discriminación en México. México, DF: CONAPRED; 2005.
33. Apinundecha C, Laohasiriwong W, Cameron MP, et al. A community participation intervention to reduce HIV/AIDS stigma,
Nakhon Ratchasima province, Northeast Thailand. AIDS Care
2007;19:1157-1165.
34. Wu S, Li L, Wu Z, et al. A brief HIV stigma reduction intervention for service providers in China. AIDS Patient Care STDs
2008;22:513-520.
35. Kudel I, Cotton S, Szaflarski M, et al. Spirituality and religiosity
in patients with HIV: A test and expansion of a model. Ann Behav Med 2011;41:92-103.
36. Muturi N, An S. HIV/AIDS stigma and religiosity among African
American women. J Health Commun 2010;15:388-401.
medicina
universitaria
www.elsevier.com.mx
Original article
Frequency of metabolic syndrome in women treated at the
Menopause Clinic of the “Dr. José Eleuterio González” University
Hospital of the UANL in Northeastern Mexico
M. Cervantes-Flores*, J. Vázquez-Méndez, D. Saldívar-Rodríguez, O. Vidal-Gutiérrez, I.
Y. González-Carrillo, G. Guerrero-González
Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de
Nuevo León, Monterrey, N. L., Mexico
Received: February 2013; Accepted: October 2013
KEYWORDS
Metabolic syndrome;
Menopause; Estrogen;
Diabetes mellitus;
Obesity; Mexico.
Abstract
Objectives: To determine the frequency of metabolic syndrome (MS) in patients with menopause, and to compare the incidence of MS between surgical and natural menopause.
Methods: This was an observational, longitudinal, descriptive, retrospective, unblinded study of
cases seen at the Menopause Clinic of the University Hospital “Dr. José Eleuterio González”
of the Universidad Autónoma de Nuevo León from March 2009 to December 2011. The frequency of MS was determined based on Adult Treatment Panel III (ATPIII) classification.
Results: At the end of the study, 391 patients were evaluated. The mean age was 50.1 years. We
found a frequency of MS of 38.1%, the risk factor most often found was low HDL-cholesterol
(62.5%), followed by obesity (46.5%), hypercholesterolemia (42.3%), hyperglycemia (11.5%), and
hypertension (7.7%).
The incidence of natural and surgical menopause was 37.6% vs. 39.2% respectively; however, the
result was not statistically significant (p = 0.093).
Conclusions: Patients with menopause are at increased risk of developing MS. It is important to
detect MS early in this of patients, when they have one risk factor to avoid complications which
may trigger the syndrome. We recommend screening for MS during perimenopause, in order to
detect and try to delay it in a timely manner and recommend primary prevention (diet and
exercise), or secondary prevention in cases with one or more risk factors.
* Corresponding author: Domingo Gayoso 240, Centro, Z.P. 64000, Monterrey, N. L., México. Telephone: (81) 1066 1243, (81) 1516 4865.
E-mail address: [email protected] (M. Cervantes-Flores).
10
Introduction
Metabolic syndrome is the coexistence of several pathologies or risk factors in a person. This cluster of conditions
increases the risk of heart disease, stroke, and diabetes mellitus. MS has several genetically determined phenotypic variances, as well as being conditioned by environmental
factors, cardiovascular disease risk factors and abdominal fat accumulation.1,2
Menopause refers to the last menstruation cycle as a consequence of the loss of activity in the ovaries. It is identified
after 12 months of amenorrhea and it only occurs in humans. The follicle-stimulating hormone, which stimulates
growth and storage of the ovarian follicles in the ovary, confirms menopause when found in blood greater or equal to 40
mU/dl. As a result of the complete cessation of ovarian
activity, 3,4 menopause can also be produced artificially
following bilateral oophorectomy, after abruptly and completely suppressing the action of the ovaries, causing a
sharp estrogen drop and losing the ovarian androgenic capacity.5
Menopause brings both hormonal and metabolic changes
that condition an increase in body weight, producing peripheral insulin resistance, rise in blood pressure, and disorders of lipid metabolism; these are the main components of
MS. Women between the ages of 17 and 24 and from 25 to
44 have a prevalence of MS of 3.8% and 16.6% respectively,
compared to women between the ages of 45 and 64 with
menopause, who show a prevalence of 35.8%.6,7
In order to diagnose MS the current consensus is based on
criteria by the National Cholesterol Education Program,
which indicates that 3 or more of the following risk factors
are required in order to make a diagnosis in women: abdominal circumference of 88 cm or body mass index (BMI) of
30 or higher; triglyceride levels higher than 150 mg/dl;
blood pressure of 130/85 mmHg; blood sugar levels greater
than 110 mg/dl, and HDL-cholesterol < 50 mg/dl.8,9
The objective of our study was to determine the frequency of MS in women with menopause.
Methods
We carried out an observational, longitudinal, descriptive,
retrospective, unblinded study of cases seen at the Menopause Clinic of the University Hospital “Dr. José Eleuterio
González” of the Universidad Autónoma de Nuevo León
from March 2009 to December 2011. We included patients
consulting for the first time, patients who had had amenorrhea for over a year, patients having undergone bilateral oophorectomy, and patients who had not received hormone
replacement therapy for at least 3 months prior to the study. We performed lab tests as well as a complete somatometry. We excluded patients who did not wish to participate
and those who did not have the required tests. We eliminated patients who abandoned the study or who did not hand
in complete lab results. We determined the existence of MS
based on the presence of 3 or more criteria of the ATPIII
classification.8,9
We created a database with collected information and
analyzed it using SPSS ® v. 20.0; we applied descriptive
M. Cervantes-Flores et al
Table 1 Metabolic syndrome risk factors and frequency.
Risk factor
Patients (n)
Percentage
Hypertension
30
7.70%
Hyperglycemia
45
11.50%
Hypertriglyceridemia
144
36.80%
Hypercholesterolemia
166
42.30%
Obesity
182
46.50%
Low HDL-cholesterol
245
62.50%
statistics to the different variables analyzed with average,
median, mode, and ranges. In addition, we analyzed
age, occupation, parity, and surgical or artificial menopause. During physical examinations, we assessed blood pressure, weight, height, and BMI, as well as lab tests, specifically
lipid profile and fasting serum glucose results. We performed a statistical analysis using Pearson’s chi square in order
to analyze the frequency of MS in patients with natural vs.
surgical menopause. We used convenience sampling. This
study was approved by the Ethics Committee of “Dr. José
Eleuterio González” University Hospital.
Results
Data from 391 patients were evaluated. The mean age was
50.1 years with a minimum of 21 and a maximum of 84. Most
patients were multiparous (73.5%, n = 28), housewives
(82.4%, n = 322), and had attended the menopause clinic as
a result of climacteric symptoms (79.3%, n = 310).
We found a frequency of MS of 38.1% (n = 149).
Only 10% (n = 43) were healthy and 50.8% (n = 199) displayed 1 or 2 criteria for MS, i.e., 1 in every 2 patients with
menopause present at the University Hospital has at least 1
MS factor.
Regarding the patients with MS, we found that 92 (23%)
displayed 3 criteria, 44 (11.27%) 4, and 17 (4.34%) 5 or more
criteria for the syndrome.
The risk factor most often found was low HDL-cholesterol
(62.5%, n = 245), followed by obesity (182 [46.5%] and patients who had a BMI greater than 30 kg/m2]. The third most
frequent factor found was hypercholesterolemia (42.3%, n =
166), followed by hypertriglyceridemia (38.3%, n = 144).
The least frequent factors were hyperglycemia and high
blood pressure (11.5% [n = 45] and 7.7% [n = 30], respectively) (Table 1).
Regarding the comparison of the incidence of MS between women with natural and surgical menopause, we
found a frequency of 37.6% (n = 49) vs. 39.2% (n = 100),
respectively; this result was not statistically significant (p
= 0.093).
Metabolic syndrome was more frequent in patients in the
fifth decade of their lives; comparing the onset of natural
versus surgical menopause we observed in the latter group
an onset at a younger age (mean age of 49.2), beginning
even in the third decade of their lives (21 years).
Frequency of metabolic syndrome in women treated at the Menopause Clinic of the
“Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico
Discussion
In recent years, MS has become more and more common
throughout the world, occuring in 25% of the population,
especially in the US and Latin America where up to one third
of the population suffers from obesity.10
We found the syndrome in over a third of our patients
(38.1%), which concurs with the literature, where an incidence of 30% to 70% is reported.10,11 Results from studies
carried out in Latin America are similar to ours. In 2011,
Tabares et al. analyzed the cases of MS in 189 postmenopausal women, finding an incidence of 31%.12 In Brazil, Albuquerque evaluated the presence of MS in pre- and
postmenopausal women, finding a similar percentage to
ours (34.7%),13 being greater in menopausal women than
those premenopausal, which concurs with the hypothesis
in this study.
When comparing in our study the frequency of MS in natural and surgical menopause, no significant differences were
found; however, the percentage was lower in the first group.
In 2008, Dorum A et al. carried out a study in Norway finding
a higher prevalence of MS in patients who had undergone
bilateral oophorectomy before 50, hence a greater risk of
heart diseases.14
Conclusion
MS is frequent among postmenopausal women attending the
Menopause Clinic of the “Dr. José Eleuterio González” University Hospital. The most frequent criteria for this diagnosis were -in order of importance-: low concentrations of
HDL-cholesterol, obesity, and hypercholesterolemia. Only a
few patients with menopause did not show any risk factor;
on the contrary, 50% showed 1 or 2 factors for this syndrome. It can be infered that these women are prone to suffer
some chronic disease; therefore, early detection and action
to reverse this condition are essential. We did not find a difference between MS frequencies in patients with natural
vs. surgical menopause; however, analysis of age groups
showed that patients who had undergone bilateral oophorectomy were younger than those with natural menopause.
We recommend screening for MS during perimenopause, to
detect and try to delay it in a timely manner, having as an
advantage the fact that this prevention is low-cost and easy
to perform.
11
Funding
References
1. Balas M, Perichart O, Pantoja L, et al. Evaluación nutricional en
mujeres mexicanas posmenopáusicas con síndrome metabólico.
Ginecol Obstet Mex 2007;75:515-526.
2. Carranza S, Guerrero L, Castro A. Frecuencia del síndrome metabólico en mujeres postmenopáusicas mexicanas y su relación
con la terapia hormonal. Ginecol Obstet Mex 2009;77:367-371.
3. Janssen I, Powell LH, Crawford S, et al. Menopause and the
metabolic syndrome: the Study of Women’s Health Across the
Nation. Arch Intern Med 2008;168:1568-1575.
4. Brantes S. Current concepts in the diagnosis of permimenopause. Medwave 2009;9(11):e464.
5. García M, Rodríguez E. Caracterización del síndrome climatérico en mujeres castradas por vía quirúrgica. Rev Cubana Obstet
Ginecol 2001;27:106-113.
6. Rocabado Urquieta EJ, Rocha Soria MI, Rivera Rojas CM, et al.
Síndrome metabólico en la menopausia. Rev Méd (Cochabamba) 2007;18:85-90.
7. Reaven GM. Banting Lecture 1988. Role of insulin resistance in
human disease. diabetes 1988:37;1595-1607.
8. Puche C, Cabero A, Meseguer A. 17 b hydroxylase activity in
human adipose tissue. European Journal of Endocrinol
2002;146:223-229.
9. González A. Consenso mexicano sobre el tratamiento integral
del síndrome metabólico. Rev Mex Cardiol 2002;13:4-31.
10. Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome:
Prevalence in worldwide populations. Endocrinol Metab Clin
North Am 2004;33:351-375.
11. Fenochio-González F. Prevalencia de síndrome metabólico en
mujeres posmenopausicas con y sin tratamiento hormonal sustitutivo. Rev Invest Med Sur Mex 2012;19:60-66.
12. Tabares-Trujillo M. Síndrome metabólico en menopausia: implicaciones de la terapia hormonal. Perinatol Reprod Hum
2012;26:25-29.
13. Albuquerque J. Síndrome metabólico y menopausia. Arq Bras
Cardiol 2010;95:339-345.
14. Dorum A, Tonstad S, Liavaag A, et al. Bilateral oophorectomy
before 50 years of age is significantly associated with the metabolic syndrome and Framingham risk score: A controlled, population-based study (HUNT-2). Gynecol Oncol 2008;109:377-383.
medicina
universitaria
www.elsevier.com.mx
Original article
Correlation between BMI and climateric symptoms in menopausal
women
I. Y. González-Carrillo*, J. Vázquez-Méndez, G. Guerrero-González, O. Vidal-Gutiérrez,
M. Cervantes-Flores
Received: February 2013; Accepted: November 2013
KEYWORDS
Climateric symptoms;
Body mass index;
Blatt-Kupperman
index; Obesity;
Mexico.
Abstract
Objectives: To determine the association between climateric symptoms and body mass index
(BMI). In addition, to define the age of onset of climateric symptoms and to associate a patient’s
occupation and marital status with climateric symptom severity.
Materials and methods: Observational, retrospective and cross-cohort study including 403 patients attending the Menopause Clinic of the University Hospital of the Universidad Autónoma
de Nuevo León from November 2008 to December 2011. Clinical history, physical examination,
weight and height, and BMI were evaluated. Climateric symptoms were assessed through the
Blatt-Kupperman modified index. Marital status and occupation were also analyzed.
Results: No relation was found between BMI and climateric severity, nor was there any relation
between climateric symptoms and marital status or occupation.
Conclusions: Additional research is needed to assess the influence of climateric risk factors.
Introduction
Menopause is the natural biological process in which a
woman’s menstrual period stops permanently. During climaterium, the progressive disappearance of the ovarian function
occurs leading to a gradual decline in estrogen secretions and
several associated hormonal alterations giving rise to a series
of organic and psychological changes. In healthy women, menopause occurs between the fifth and the sixth decades of
life (from ages 47 to 52).1 Climateric symptoms worsen in relation to social determinants linked to race, social and cultural entitlements which fall upon their gender.2
The manifestations produced as a consequence of the ovarian function ceasing and the subsequent hormonal deficit,
* Corresponding author: Laguna de Catemaco 1359, Las Quintas, Z.P. 80060, Culiacán, Sin., Mexico. Telephone: (667) 715 8045. E-mail
address: [email protected] (I. Y. González-Carrillo).
Correlation between BMI and climateric symptoms in menopausal women
are expressed with very unique symptoms known as climateric.1-3 In order to evaluate climateric symptoms, different
scales have been developed, for instance the Kupperman
index,4 the Utian Quality of Life (UQOL) Scale,5 the Greene
scale,6 and the SUMEVA scale.7 Some assess the impact of
climateric symptoms in the quality of life, especially the
influence on perimenopausal patients, this information
being useful in the follow-up of patients who receive hormone replacement treatment (HRT).8
Hypoestrogenism has been related to physiological changes which are, in part, responsible for the weight gain during that period.9 In Mexico, an overweight prevalence of
72% in adult women has been reported.10
Obesity in connection with vasomotor symptoms is controversial. Previous studies suggest that body fat protects
women from vasomotor symptoms due to the aromatization
of androgens to estrogens in the adipose tissue; however,
other evidence suggests that a greater body mass index
(BMI), and increased body fat in particular, are associated
with reports of greater climateric manifestations.11,12 In this
study we assess the hypothesis that there is a correlation
between BMI and the severity of climateric symptoms, studying overweight (according to BMI) connection with climaterium, through the Blatt-Kupperman index,4 with the purpose
of determining whether or not obese or overweight patients
suffer from more severe climateric symptoms.
Materials and methods
An observational, retrospective, descriptive, cross-cohort
study was described. We included 431 patients who attended the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de
Nuevo León, in Monterrey, N. L., Mexico, from November
2008 to December 2011. Patients who had received HRT during the previous 3 months and those who did not comply
with the required data were excluded.
We performed a full clinical history check in order to obtain personal data and background information, a physical
examination including measurement of height and weight to
obtain BMI and a questionnaire on climateric symptoms
through the Blatt-Kupperman modified index.5 The BlattKupperman index is a scale used to determine the severity
of climateric symptoms; it assesses 15 symptoms, which are
rated by the patients as follows: 0 = none, 1 = mild, 2 = moderate, 3 = severe.
Subsequently, a score was obtained which was categorized as mild (0-20), moderate (21-35), or severe (> 35).13 The
variables included were: Age, marital status, occupation,
BMI, number of years of menopause, and modified BlattKupperman index.
With the data obtained we created a database in Microsoft Excel®, for subsequent analysis using SPSS® v. 14. All the
variables were analyzed with traditional descriptive statistics such as statistical average and dispersion measures
(standard deviation). Pearson’s correlation test was used to
assess the correlation between BMI and Blatt-Kupperman, as
well as a dispersion graph. Using Pearson’s correlation, a
value of -1 to 1 was obtained (a value closer to 1 indicates
a positive correlation while a value closer to -1 indicates a
negative correlation; if the value is close to 0, it implies
13
that there is no lineal relation). We assessed the correlation
between marital status and occupation with the Blatt-Kupperman index through Pearson’s R test.
Results
A total of 403 patients with an average age of 50.01 (± 7.70)
years, with an average of 5.69 (± 5.97) years of menopause
were included in the study. The average BMI was 28.98 (±
5.71) kg/m2. The average value of the Blatt-Kupperman index was 25.78 ± 13.48. Regarding marital status, 334 (83%)
of the patients were married, 52 (13%) were single, and 17
(4%) were widows. Three hundred forty-nine patients (87%)
were housewives, 42 (10%) were employed outside their homes and 12 patients (3%) were retired.
We found that the symptoms in 113 patients (28%) were
rated as severe, in 140 (35%) as moderate, and in 150 (37%)
as mild, according to the Blatt-Kupperman index.
Concerning BMI and degree of obesity, 0.3% of the patients were thin, only 20.1% had what is considered to be a
normal BMI, 41.0% were overweight, and 37.7% were obese.
We evaluated the correlation between BMI and the BlattKupperman index through Pearson’s R test, obtaining a value of 0.053; consequently, we did not find a relationship
between these 2 variables.
In order to show a correlation between BMI and the BlattKupperman index, a dispersion graph was created; no correlation was found since we were not able to see an increasing
or decreasing tendency of the Blatt-Kupperman index regarding BMI (Fig. 1).
We evaluated the relationship between marital status
and occupation with the Blatt-Kupperman index, through
Pearson’s R test, with a value of -0.074 and 0.017 respectively;
therefore, no relationship was found between these variables.
Discussion
The information regarding the association between BMI and
climateric symptoms is controversial. In this study we assessed the correlation between the degree of obesity and the
Blatt-Kupperman index, since some authors concur that estrogen production in adipose tissue in overweight and obese
patients protects them from suffering climateric symptoms,9 in contrast with other authors who conclude that a
greater BMI and weight gain are associated with reports
of greater climateric manifestations, mainly hot flashes, during transition to menopause. These findings concur with a
thermoregulatory model of vasomotor symptoms in which
body fat acts as an insulator, preventing heat dissipation.14
Riley et al. found that 30% of 468 perimenopausal and 287
postmenopausal females reported hot flashes. Perimenopausal patients with a BMI > 25 kg/m2 reported more hot
flashes with a relative risk (RR) of 2.00 (RI 95% = 1.28 3.12). We did not find an association with hot flashes in
postmenopausal patients.15
Martínez Pérez et al. carried out a study with 10,514 women with an average age of 57.9 (± 7.1) years, finding that
smoking, use of alcohol, BMI > 25 kg/m2, marital status,
educational level, and social level were associated with
more severe menopausal symptoms for BMI (RR = 3.64; RI
95% = 2.96 - 4.32).16
14
I. Y. González-Carrillo et al
presenting symptoms and to develop appropriate preventative strategies, including lifestyle modifications and the establishment of better treatment.
70
60
50
40
30
Funding
20
10
0
0
100
200
Blatt Kupperman
300
400
500
BMI
Figure 1 Dispersion chart between BMI and the Blatt-Kupperman index.
Thurston et al. assessed the connection of the adiposity
with vasomotor symptoms in the study of Women’s Health
Across the Nation, which included 1,776 women aged 47 to
59 years with an intact uterus and at least 1 ovary, in whom
vasomotor symptoms and hormonal serum levels were evaluated. They concluded that a greater percentage of body
fat was associated with vasomotor symptoms (RR = 1.27; RI
95% = 1.14 - 1.42).17
In this study, no connection between BMI and Blatt-Kupperman index was found; a probable reason for this is the
fact that estrogens of peripheral origin do not have the biological action that ovarian estrogen has.
The reason for the inconsistent findings regarding a connection between BMI and climateric symptoms is unknown.
Some studies suggest that the inconsistencies may be related to the different endogenous estrogen and other hormones levels in women with different body sizes. Hormonal
changes are customary during the transition into menopause. Furthermore, for the formation of estrogens from circulating androgen precursors, the adipose tissue produces
hormones such as leptin and tumor necrosis factor, which
suppress ovarian production of steroids and have an influence on thermoregulation.18
Pérez-Pérez found that women who work in public spaces
adapt more easily to hormonal changes in climaterium and
menopause, in contrast to those who are housewives who
feel misunderstood, rejected, and have a low self-esteem.19
However, no connection was established between the BlattKupperman index and occupation or marital status in our
study. Further studies assessing all risk factors, like health
problems, use of alcohol, smoking, role at work, family dynamics, presence of depression, as well as their connection
with weight gain or loss in the female in transition to menopause are required.
While the results of this study report that the degree of
obesity does not have an impact on climateric symptoms
severity, most patients showed some degree of overweight
or obesity; hence obese patients should undergo more complete tests, including sociological, physical, and personal history, in order to identify those with a higher risk of
References
1. Accessed in January 2014. http://www.consultorsalud.com/biblioteca/Guias/Menopausia.pdf
2. Accessed in January 2014. http://www.scog.sld.cu/Articulos/
consenso2006seccclimymenop.pdf
3. Accessed in January 2014. http://www.docstoc.com/
docs/74212096/The-Menopause-Handbook
4. Kupperman HS, Wetchler BB, Blatt M. Contemporary therapy of
the menopausal syndrome. JAMA 1959;171:103-113.
5. Utian WH, Janata JW, Kingsberg SA, et al. The Utian Quality of
Life (UQOL) scale: development and validation of an instrument to quantify quality of life through and beyond menopause. Menopause 2002;9:402-410.
6. Greene JG. Construcción de una escala climatérica estándar.
Rev Climaterio 1998;1:292-301.
7. Carranza LS, Reyes RP, Chan VR. SUMEVA, a new system of climateric symptom evaluation, and its correlation with FSH and
estradiol levels. Int J Fertil Womens Med 2006;51:140-144.
8. Carranza LS, Cruz Sánchez K. Relación entre síntomas del climaterio y la calidad de vida. Ginecol Obstet Méx 2008;76:703705.
9. Pavón de Paz I. Obesidad y menopausia. Nutrición Hospitalaria
España 2006;21:633-637.
10. Díaz Villaseñor A. La obesidad en México. Salud Pública. México: Fundación Este País; 2011. p. 61-64.
11. Lambrinoudaki I, Brincat M, Erel CT, et al. EMAS position statement: Managing obese postmenopausal women. Maturitas Grecia 2010;66:323-326.
12. Thuston RC, Sowers MR, Sternfeld B, et al. Gains in body fat
and vasomotor symptom reporting over the menopausal transition. Am J Epidemiol 2009;170:766-774.
13. Casado Méndez PR, Arró Martínez Y, Arias Hernández D. Repercusión del tabaquismo pasivo en el síndrome climatérico. Rev
Cubana Hig Epidemiol 2012;50:1-10.
14. Schwingl PJ, Hulka BS, Harlow SD. Risk factors of menopausal
hot flashes. Obstet Gynecol 1994;84:29-34.
15. Hyde Riley E, Inui TS, Kleinman K, et al. Differential association
of modifiable health behaviors with hot flashes in perimenopausal and postmenopausal women. J Gen Intern Med 2004;19:740746.
16. Martínez JA, García FC, Palacios S, et al. Epidemiology of risk
factors and symptoms associated with menopause in Spanish
women. Maturitas 2009;62:30-36.
17. Thurston RC, Sowers MR, Chang Y, et al. Adiposity and reporting
of vasomotor symptoms among midlife women. Am J Epidemiol
2008;167:78-85.
18. Whiteman MK, Staropoli CA, Benedict JC, et al. Risk factors for
hot flashes in midlife women. J Womens Health 2003;12:459472.
19. Pérez-Pérez R, Medina Barragán RA, Espiricueta-Medina M. Respuestas adaptativas de mujeres en climaterio y menopausia.
Rev Enferm Inst Mex Seguro Soc 2011;19:123-126.
medicina
universitaria
www.elsevier.com.mx
Original article
Infiltration vs. instillation of ropivacaine 7.5% in radical
mastectomies for postoperative analgesia
B. I. Yolanda-Prieto*, A. L. Millán-Corrales, D. Palacios-Ríos, B. I. Garduño-Chávez, N. G.
López-Cabrera, G. A. Millán-Cornejo, B. T. González-Rocha
Department of Anesthesiology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León,
Monterrey, N. L., Mexico
Received: June 2013; Accepted: October 2013
KEYWORDS
Radical mastectomy;
Ropivacaine;
Infiltration;
Instillation; Mexico.
Abstract
Objective: Determining the effectiveness of infiltration versus instillation with 7.5% ropivacaine
in reducing the intensity of postoperative pain in patients undergoing a radical mastectomy.
Material and methods: Clinical, prospective, and comparative analytical study in a sample of 20
female patients between 20 and 60 years of age, ASA I and II, weight 50-90 kg, who were divided
into 2 groups (10 patients each). In Group 1 infiltration with ropivacaine 7.5% (20 ml) was
applied prior to closure of the surgical wound, meanwhile in Group 2 ropivacaine 7.5% (20 ml),
was instilled into the surgical wound. Pain intensity was assessed by a visual analog scale (VAS)
upon extubation. The need for rescue medication and the incidence of nausea and vomiting
were measured from 0 to 30 minutes postoperatively and at 2, 4, 8 and 12 hours.
Results: There was no statistical difference between the groups (only the group managed
through infiltration required rescue medications), but the infiltration group had a lower perception of pain.
Conclusions: This study reported the same efficacy of preventive treatment of postoperative
pain in patients who underwent radical mastectomy for instillation and infiltration with 7.5%
ropivacaine and little need for rescue medication postoperatively.
Introduction
Preventive analgesia was described by Crile in 1913 as an option to prevent alterations in the autonomic nervous system
resulting from postoperative pain, based in regional blocks
with local and general anesthetics. 1 Initially, preventive
analgesia for postoperative pain treatment was not well accepted, due to controversial results in experimental and
* Corresponding author: Department of Anesthesiology, University Hospital “Dr. José Eleuterio González”. Francisco I. Madero, Mitras
Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: (+01) 8389 1136. E-mail address: [email protected],
[email protected] (B. I. Yolanda-Prieto).
16
B. I. Yolanda-Prieto et al
clinical research work; however, nowadays its use is being
reconsidered.2-5
Underestimated postoperative pain by medical personnel
as well as lack of knowledge and adherence to a multimodal
analgesic management, are factors accounting for an inadequate therapeutic management of postoperative patients.
This has a direct impact on the patient’s optimal recovery,
in addition to allowing the development of chronic complications following the surgical procedure. Studies published
in recent years show a prevalence of moderate to unbearable pain of 11% (in a hospital with an acute postoperative
pain unit), and in 70% of the patients who have undergone
surgery during the first 24 to 48 hours; nevertheless, prevalence has always exceeded 30%.6
There are surgical procedures such as mastectomies in
women, which besides producing pain may cause diverse
emotional reactions.7 Breast cancer is one of the 2 most
common malignancies in women worldwide and the main
treatment for this pathology is surgery.7-10
Despite different therapeutic approaches with several
analgesics and routes of administration to avoid pain, the
desired analgesic effect is not accomplished in some patients; a reason for this could be the route of administration
used or the fact that the strength of the medication may be
insufficient.
Radical mastectomy is an extensive and disfiguring procedure, which causes acute postoperative pain due to soft tissue injury of the anterior wall of the thorax. During
dissection, tissue traction takes place producing damage to
the axons of the intercostal nerves and brachial plexus emergence. There are several anesthetic strategies; some of the
most commonly utilized are intercostal nerve blocks, preoperative thoracic epidural block, thoracic paravertebral block,
local infiltration blocks, and direct instillation.11-13
Instillation is the introduction of a liquid (by pouring or
injection), drop by drop over mucous membranes or the
skin. It is a very commonly used method. Postoperative infiltration (direct administration of the analgesic into the surgical area), as a strategy for pain management in this
pathology has not been studied extensively and is underconsidered regarding patient management, hence this study.
We carried out a comparison between these 2 local analgesic administration techniques by means of a pain scale and
the use of rescue medication; by doing so, we attempted to
decrease the endocrine response caused by pain and the
side effects in the cardiopulmonary and immunology
functions that patients with postoperative pain suffer.14
Material and methods
We included female patients scheduled for radical mastectomy at “Dr. José Eleuterio González” University Hospital of
the Universidad Autónoma de Nuevo León (UANL), Mexico. The patients agreed to participate in the study by signing an informed consent form. We obtained demographic
variables such as age, weight and relevant background. Patients were divided into 2 groups; in Group 1 infiltration
with ropivacaine 7.5% (20 ml) was applied prior to closure of
the surgical wound, while in Group 2 ropivacaine 7.5% (20
ml) was instilled into the surgical wound. Inclusion criteria
required patients to be between 20 and 60 years of age, to
have a weight between 110 and 198 lb (50-90 kg), ASA I or II,
to be scheduled for radical mastectomy, and have preoperative test results within normal limits. Patients with a history
of coagulopathy, radiotherapy, neurological alterations, and
previous analgesic or antiinflammatory treatment were excluded. Subsequently, we assessed blood pressure, heart
rate, respiratory rate, and pain using a visual analogue scale
(VAS) in both groups; in addition the presence of nausea
and/or vomiting was measured from 0 to 30 minutes postoperatively and 2, 4, 8, and 12 hours afterwards.
Data was inputted into a database created in Excel® 2010
and analyzed using IBM® Statistic 21; for the quantitative variables, traditional descriptive statistics, measures of central tendency, dispersion and position, as well as the observed
frequencies in the qualitative variables were calculated. The
values were verified by group through hypothesis tests for median and proportion, according to each variable type (quantitative and qualitative respectively) with a reliability of 95%.
Results
Average age was 49.7 ± 7.8 years for Group 1 (infiltration)
and 43.8 + 12.5 years in Group 2 (instillation); there was no
significant difference in both groups (p = 0.2234). Average
weight was 71.4 kg ± 9.7 for Group 1, and 65.4 ± 14.3 for
Group 2; we did not find significant differences between the
groups (p = 0.2863).
Regarding ASA classification, 50% of the patients in Group
1 and 60% in Group 2 presented with ASA I; the rest of the
patients in both groups were ASA II. We did not observe a
statistically significant difference regarding vital signs in
either group (Tables 1 and 2). No presence of nausea
in either group was observed.
Table 1 Systolic blood pressure comparison in both groups.
Baseline
Mean (SD)
30 min
Mean (SD)
2 hours
Mean (SD)
4 hours
Mean (SD)
8 hours
Mean (SD)
12 hours
Mean (SD)
Group 1
n = 10
128.70 (24.10)
124.80 (15.50)
125.80 (12.49)
124.10 (13.99)
120.70 (13.28)
120.50 (13.44)
Group 2
n = 10
126.40 (16.41)
120.00 (20.63)
121.50 (19.26)
123.10 (16.46)
117.80 (12.95)
119.20 (13.09)
NS
NS
NS
NS
NS
NS
N = 20
p
Infiltration vs. instillation of ropivacaine 7.5% in radical mastectomies for postoperative analgesia
17
Table 2 Diastolic blood pressure comparison in both groups.
Baseline
Mean (SD)
30 min
Mean (SD)
2 hours
Mean (SD)
4 hours
Mean (SD)
8 hours
Mean (SD)
12 hours
Mean (SD)
Group 1
n = 10
73.10 (14.12)
69.20 (9.94)
73.20 (7.21)
77.60 (9.51)
71.60 (9.87)
71.70 (9.61)
Group 2
n = 10
72.10 (8.02)
70.50 (15.41)
72.80 (11.89)
71.80 (7.90)
72.20 (10.70)
70.90 (7.99)
NS
NS
NS
NS
NS
NS
N = 20
p
10.00
9.00
8.00
7.00
VAS
6.00
5.00
4.00
3.00
2.00
1.00
0.00
VAS 0 VAS 30
min
min
VAS 2
hrs
VAS 4
hrs
VAS 8
hrs
VAS 12
hrs
Installation
Figure 1 Visual analog scale.
Regarding the VAS results, Group 2 showed better results in all of the evaluation periods, except at 12 hours
when results were better in Group 1; however, such differences did not prove to be statistically significant (Fig. 1).
A higher number of rescue medication (dexketoprofen 50
mg intravenously [IV]) for Group 1 at 30 minutes and 4
hours was required. In addition, 1 patient from Group 1
required buprenorphine as rescue medication, as she failed to show a decrease in pain. Neither group showed side
effects.
Discussion
When cross-referencing both groups, no differences were
seen; in both cases the behavior of the variables was the same statistically, mainly concerning pain, except for the group
managed with infiltration requiring rescue medication. Despite advances in the knowledge of pain and the constitution of
Algology as a new specialty, postoperative pain is frequent in
patients after a surgical procedure; if avoided; side effects
may be prevented.15-18
Most clinical research studies on preventive analgesia in
patients who undergo radical mastectomy refer to spinal
blocks. Epidural anesthesia has also been evaluated as
anesthesia and management of acute pain during the performance of the mastectomy; yet in the present study we
decided not to use it for anesthetic purposes, given the
fact that it must be placed in the metamers between C
VII y D IV. The puncture of the intervertebral spaces in
this region is technically difficult and the position the patient must assume in order to place it may increase the
anxiety that involves a morbidity risk due to ventilation
problems; this increases if there is a need to sedate the
patient.19
Infiltration of the wound and instillation of local anesthetics is another simple and effective technique providing
pain relief during the early postoperative period following surgical procedures. There are studies indicating that
ropivacaine infiltration on the surgical wound after surgery
reduces pain intensity, reducing the requirement of postoperative analgesics and inpatient days. In addition, the
amount of applied anesthetics and its absorption through
the peritoneal surface provide an additional mechanism of
analgesia.
Multiple studies have been performed in order to demonstrate the clinical safety of ropivacaine in animals as well as
in humans (5 mg/ml IV infusions).19 The literature reports
few studies on instillation and infiltration of ropivacaine
7.5%; thus, having found similar results with this route of
administration in the present study, it is recommended as
an alternative for optimal postoperative analgesia in patients who undergo radical mastectomy. Incidence of nausea
and vomiting, if any, is low.
We found that ropivacaine infiltration or instillation in
the surgical wound prior to skin closure showed no significant difference on postoperative pain (except for the
necessity of using rescue medication in the infiltrated
analgesic group); this was proven when cross-referencing
VAS recordings at 2, 4, 8 and 12 postoperative hours between each group (p > 0.05 in every crossing); however,
when looking at the numerical behavior, lower values of
pain in the “infiltration” group were found. Nevertheless,
this could also be caused by the use of rescue medications;
in addition, the patient’s resistance to the analgesic can
also be a variable presented at random. Consequently, the
use of a larger sample for future related studies should be
the next step, with the purpose of increasing the statistical value in search of establishing whether or not there is
a significant difference.
18
Conclusions
No statistical difference was found between the use of ropivacaine 7.5% infiltrated or instilled in patients undergoing
radical mastectomy.
Funding
References
1. González ML, Martínez MA, Ramírez ML. Opciones analgésicas
para el control del dolor posterior a mastectomía radical. Cir
Ciruj 2004;72:363-368.
2. Katz J. Preemptive analgesia. Anesthesiology 2002;77:439-446.
3. Kissin I. Preemptive analgesia: why its effect is not always obvious. Anesthesiology 1996;84:1015-1019.
4. McCartney CJ, Sinha A, Katz J. A qualitative systematic review
of the role of N-methyl-D-aspartate receptor antagonists in
preventive analgesia. Anesth Analg 2004;98:1385-1400.
5. Leach A. Old ideas, new applications. Br J Anesth Anaesthesiol
1998;89:500-506.
6. Soler E, Faus MT, Montaner MC. Servicio de farmacia. El dolor
postoperatorio en la actualidad: un problema de calidad asistencial. Hospital francesc de Borja de Gandía y Departamento
de Farmacología de la Universidad de Valencia. 2000;24:123135.
7. Bard M, Sutherland AM. Psychological impact of cancer and its
treatment. Adaptation to radical mastectomy. Cancer
1995;8:652-672.
B. I. Yolanda-Prieto et al
8. Perkins GH, Middleton L. Breast cancer in men. Br Med J
2003;327(7409):238-240.
9. Secretaría de Salud. Dirección General de Estadística e Informática. Incidencia y prevalencia de cáncer en México. Salud
Publica Mexico 2006;38:75-81.
10. Borgen PI, Wong GY, Vlamis V. Current management of male
breast cancer: a review of 104 cases. Ann Surg 2002;215:451459.
11. Belfer I, Wu T, Kingman A, et al. Candidate gene studies of human pain mechanisms. Anesthesiology 2004;100:1562-1572.
12. Prithvi R. Tratamiento práctico del dolor. Estados Unidos de
América. Mosby/Doyma;1995. p. 7.
13. Arner S, Meyerson BA. Lack of analgesic effect of opioids on
neuropathicand idiopathic forms of pain. Pain 1998;33:11-23.
14. Rodríguez OL. Anestesia local en cirugía oral y maxilofacial.
Parte I, Hospital General Docente “Aleida Fernández Chardiet”. Revista de Ciencias Médicas La Habana 1999;5(2).
15. Suresh S, Barcelona SL, Young NM, et al. Does a preemptive
block of the great auricular nerve improve postoperative analgesia in children undergoing tympanomastoid surgery? Anesth
Analg 2004;98:330-333.
16. Wurm WH, Concepción M, Sternlicht A, et al. Preoperative interscalene block for elective shoulder surgery: loss of benefit
over early postoperative block after patient discharge to home.
Anesth Analg 2003;97:1620-1626.
17. Marret E, Flahault A, Samama C, et al. Effects of postoperative,
nonsteroidal, antiinflammatory drugs on bleeding risk after
tonsillectomy. Meta-analysis of randomized, controlled trials.
Anesthesiology 2003;98:1497-1502.
18. Beilin B, Shavit Y, Trabekin E, et al. The effects of postoperative pain management on immuneresponse to surgery. Anesth
Analg 2003;97:822-827.
19. Bromage P. Analgesia peridural. España: Editorial Salvat; 1984.
p. 335-387.
20. Lewis CD. Control of postoperative pain. Nonnarcotic and narcoticalternatives and their effect on pulmonary function. Chest
1987;92:520-527.
medicina
universitaria
www.elsevier.com.mx
Original article
Maternal mortality and severe obstetric morbidity in a tertiary
care hospital
J. L. Iglesias-Benavides*, M. S. Vidales-Hernández, W. E. Treviño-Ledezma, S. N.
Delgado-Muñiz, A. Guzmán-López
Received: October 2013; Accepted: October 2013
KEYWORDS
Maternal death;
Severe obstetric
morbidity; Incidence;
Mexico.
Abstract
Introduction: Maternal mortality (MM) is a reflection of the quality of care given to pregnant
women. However, it does not reflect many illnesses and medical complications of women at risk
of death, who do not die. Severe obstetric morbidity (SOM) refers to women who are “pregnant
or recently postpartum, very ill, who would have died if not for the good health care received”.
Objective: To review the incidence of MM and SOM at the Obstetric Service of the University
Hospital, Universidad Autónoma de Nuevo León (UANL) in the years 2007-2011.
Material and methods: Observational, cross-sectional, retrospective study, at the Obstetric Service of the University Hospital, UANL.
Results: We attended 19,985 births; there were 37 maternal deaths: 14 due to hypertensive
disorders (37.8%), 3 due to hemorrhage (8.1%), 13 (35.1%) due to medical complications, 1
(2.7%) due to an anesthetic problem, and 6 due to sepsis (16.2%). Twenty-three (62.1%) maternal deaths were catalogued as direct and 14 (37.8%) as indirect. Of 407 cases of SOM, 310
(76.1%) were due to hypertensive disorders, 58 (14.2%) to obstetric hemorrhage, 26 (6.3%) to
medical complications, 1 (0.2%) to anesthetic complication, and 12 (2.9%) to sepsis. The MM
rate was 1.85 per 1,000 live births; the incidence of MOS was 81.4 per year, with 1 death per
every 11 cases.
Conclusions: The MM and the SOM provide more reliable data on the prevalence of serious complications in obstetrics. This allows us to take preventive measures, offer better medical care,
and improve the allocation of resources.
* Corresponding author: Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital. Madero y Gonzalitos
Avenue, Mitras Centro, Monterrey, N. L., México. E-mail address: [email protected] (J. L. Iglesias-Benavides).
20
Introduction
Maternal mortality (MM) is an occurrence which reflects the
quality of the healthcare system. The World Health Organization defines maternal death as “the death of a woman
while pregnant or within 42 days of termination of pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes”. Direct maternal death is the result of a
complication of the pregnancy, delivery or management of
the 2 while an indirect maternal death (IMD) is a pregnancyrelated death in a patient with a preexisting or newly developed health problem unrelated to pregnancy. The standard
indicator is the MM rate which is defined as the relationship
between the numbers of maternal deaths for every 1,000
births.1
Severe obstetric morbidity (SOM) refers to “a pregnant or
postpartum patient, very ill, who if not treated appropriately, would result in death”.2 It is safe to assume that the
same disease processes which cause SOM are closely related
to the ones which cause MM. It is possible to study the circumstances surrounding women with SOM, therefore we are
able to implement a better surveillance on maternal care.3
In medical literature, different inclusion criteria are used
in the selection of SOM cases such as acute organ system
dysfunction,4 severe obstetric complications between the
28th week of gestation and 42 days of puerperium,5 admissions to the intensive care unit,6,7 patients receiving a blood
transfusion,8 and anesthetic accidents.9
The MM rate and other indexes have been created as a
result of the study of such data. These indexes provide a better understanding of the medical problems surrounding
pregnant women. Mortality rate represents the number of
deaths in accordance to the number of SOM cases, morbidity rate expresses the relationship between SOM cases for
every maternal death, and SOM incidence indicates the
number of very ill women who are attended per year.10-13
The objective of this study was to review the main causes
and incidence of maternal death, as well as SOM at the “Dr.
José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo León (UANL), between 2007 and
2011. Another objective was the analysis of medical and social factors related to the care and attention of obstetric
complications and maternal deaths.
Material and methods
In this retrospective, transversal, analytic study, files of patients classified as maternal death, and those who met the
criteria for SOM between January 2007 and December 2011
were reviewed.
According to the literature, we considered as SOM pregnant women with severe preeclampsia, eclampsia and
HELLP syndrome (a life-threatening pregnancy complication
usually considered to be a variant of preeclampsia, named
after its characteristics: hemolysis, elevated liver enzymes,
and low platelet count); women who had hemorrhage before, during or after delivery higher than 500 ml and who
required a blood transfusion; severe medical diseases complicating pregnancy (cardiomyopathy, nephropathy, AIDS,
thrombocytopenic purpura, etc.); women admitted to the
J. L. Iglesias-Benavides et al
intensive care unit who underwent an obstetric hysterectomy, laparotomy or pelvic packing, as well as anesthetic
accidents and puerperal sepsis cases.4-9
In order to obtain a better data analysis of MM and SOM,
we divided the patients into 5 groups: hypertensive disorders, obstetric hemorrhage, medical conditions, anesthetic
accidents, and sepsis.
The studied variables were: discharge diagnosis, number
of surgeries practiced, blood transfusions, age, schooling,
marital status, prenatal care (5 visits or more), gestational
age, days of overnight stay, admittance to the Neonatal Intensive Care Unit (NICU -UCIN in its Spanish acronym) and
newborn conditions (NB). We calculated the MM rate (number of maternal deaths over the number of live births and
stillbirths per 1,000),10 the mortality rate (maternal deaths
over the number of SOM cases times 100)11,12 morbidity rate
(number of SOM cases divided by the number of maternal
deaths) and SOM incidence (number of SOM cases over the
sum of periods of time).13,14 We performed descriptive statistics of frequency.
Results
During the 5-year reviewed, 19,985 births took place and
37 maternal deaths were registered (0.18%). The causes of
death were as follows: 14 corresponded to hypertensive
disorders (37.8%), 3 to hemorrhage (8.1%), 13 to medical complications (35.1%), 1 to an anesthetic problem
(2.7%), and 6 to sepsis (16.2%) (Table 1). In 23 of the cases
(62.1%), maternal death was classified as direct and in 14
(37.8%) as indirect. Maternal death rate was 1.85 per
1,000 born alive and dead. We gathered 407 SOM cases:
310 (76.1%) hypertensive disorders, 58 (14.2%) with an
obstetric hemorrhage, medical complications in 26 (6.3%),
1 case (0.2%) with anesthetic complications, and 12 (2.9%)
with sepsis (Table 2). Mortality rate was 9.09% and morbidity rate resulted in 1 death for every 11 SOM cases (Table
3). SOM incidence was 81.4 cases per year. After measuring mortality and morbidity rates within each of the SOM
pathology groups, we found that for hypertensive disorders, morbidity rate resulted in 1 death for every 22.1
cases and mortality was 4.5%; in the hemorrhage cases,
morbidity rate resulted in 1 death for every 19.3 and mortality was 5.1%; regarding medical complications and sepsis, morbidity rate resulted in 1 death for every 2 and
mortality was 50%; for anesthetic complications, morbidity rate was a single case which resulted in death with a
mortality rate of 100% (Table 4).
Sixty patients underwent hysterectomy (14.7%) and 56 files were reviewed. Background of a previous C-section occurred in 34 cases (60.7%). The diagnosis corresponded to
placenta accrete in 30 cases (53.5%), uterine atony in 12
(21.4%), cornual and cervical ectopic pregnancy in 3
(5.35%), uterine myomatosis in 3 (5.35%), uterine perforation in 3 (5.35%), and 3 (5.35%) cases with sepsis. In 2
patients a carcinoma in situ diagnosis was established. In
52 patients (92.8%) blood transfusion was required, ranging
from 1 to 25 blood packs with an average of 4.3; fresh frozen plasma was applied in a range between 1 and 40 with an
average of 3.8; platelets concentrates were applied in a
range between 1 and 33 with an average of 4.4.
Maternal mortality and severe obstetric morbidity in a tertiary care hospital
21
Table 1 Causes of maternal deaths from 2007 to 2011.
Maternal death causes
2007
2008
2009
2010
2011
Total
%
Hypertensive disorders
2
2
4
0
6
14
37.8
Obstetric hemorrhage
2
0
1
0
0
3
8.1
Medical condition
3
1
5
3
1
13
35.1
Anesthetic complication
0
1
0
0
0
1
2.7
Sepsis
2
1
3
0
0
6
16.2
Total
9
5
13
3
7
37
99.9
Table 2 Number of cases of severe obstetric morbidity from 2007 to 2011.
Severe obstetric morbidity
2007
2008
2009
2010
2011
Total
%
61
57
39
64
89
310
76.1
18
6
13
10
11
58
14.2
Medical condition
4
2
10
5
5
26
6.3
Anesthetic complication
0
1
0
0
0
1
0.2
Sepsis
4
1
3
2
2
12
2.9
Total
87
67
65
81
107
407
99.7
Table 3 Relation between number of births, morbidity, severe obstetric morbidity (SOM), maternal deaths and associated data
of the period 2007-2011.
Year
Births
SOM
Maternal deaths
Mortality rate (1,000
newborns)
Morbidity rate
Mortality index (%)
2007
3,890
87
9
2.31
9.6
10.3
2008
3,915
67
5
1.27
13.4
7.4
2009
3,718
65
13
3.49
5
20
2010
4,074
81
3
0.73
27
3.7
2011
4,388
107
7
1.59
14.5
6.8
Total
19,985
407
37
1.85
11
9.09
Admittance to the NICU occurred in 132 cases (32%) as follows: 80 due to hypertensive disorders (19.6%), 20 due to
hemorrhage (4.9%), 24 due to a medical condition (5.8%) and
8 due to sepsis (1.96). Hospital stay ranged from 5 to 90 days,
with an average of 10 days.
Maternal age was analyzed in 368 cases and ranged from 14
to 42 years, with an average of 25.3. The most frequent age
group was under 20 years with 128 cases (34.7%), followed by
21 to 25 years with 81 (22%). As for marital status, the distribution of the 327 cases was as follows: 195 single or in common-law marriage (59.6%) and 132 married (40.3%). Schooling
for the 327 cases was: 56 with elementary school completed
(17.1%), 193 with junior high school completed (59.02%), and
78 with high school or higher education completed (23.8%)
(Table 5). Distribution by gestational age in weeks at the moment of admission was, out of the 327 SOM patients: of 43
cases with 25-30 weeks of age; 93 cases between 31-35 weeks (28.44%); 181 between 36-40 weeks (55.35%), and 10 cases
with 41 weeks or more (3.05%). Prenatal care in 327 files was
considered positive in 233 cases (71.2%) and negative in 94
(28.7%). Obstetric care in 354 reviewed cases was of 3 uterine curettage (0.84%), 38 deliveries (10.73%) and 313 C-sections (88.41%).
22
Table 4 Relation between severe obstetric morbidity, maternal deaths, mortality rate and morbidity rate for each group.
Severe obstetric morbidity
N
Maternal deaths (n)
Morbidity rate
Mortality rate (%)
310
14
22.1
4.5
58
3
19.3
5.1
Medical condition
26
13
2
50
Anesthetic complications
1
1
1
100
Sepsis
12
6
2
50
Total
407
37
11
9.09
Table 5 Maternal age, marital status and level of education frequencies in severe obstetric morbidity patients between 2007
and 2011.
Maternal age
2007
2008
2009
2010
2011
Total
(%)
< 15
4
0
2
4
6
16
4.3
16-20
16
27
14
33
38
128
34.7
21-25
22
11
11
14
23
81
22
26-30
12
5
9
8
11
45
12.2
31-35
17
14
10
10
13
64
17.3
36-40
7
4
4
6
7
28
7.6
> 40
2
1
1
1
1
6
1.6
Total
68
62
51
76
99
368
99.7
Married
29
28
16
28
31
132
40.3
Single/
common-law
marriage
43
28
30
34
60
195
59.6
Total
72
56
46
62
91
327
99.9
Elementary
12
10
10
10
14
56
17.1
Junior high
school
45
34
20
40
54
193
59.02
High school
or
higher
15
12
16
12
23
78
23.8
Total
72
56
46
62
91
327
99.9
Marital status
Level of education
Discussion
Maternal mortality is the result of a series of events which
reveal a lack of action to improve the conditions and the
exclusion conditions which many women in Mexico live in.
Behind every maternal death there is a series of severe socioeconomic problems such as a high child morbidity/mortality rate, malnutrition, orphanage, schooling drop-outs,
and a premature start for children in the workforce.15 MM is
a reflection of the quality of care given to pregnant women.
However, this parameter does not show the frequency of
many of the pathologies of women who were close to dying
but survived. The undeniable benefits of this knowledge
allow us to know what is really happening in the obstetric
units, while MM provides us with limited information.
Around 1% of pregnant women suffer some sort of event
which puts their lives at risk and there is an estimate of 120
events for every direct MM, most of which are related to
Maternal mortality and severe obstetric morbidity in a tertiary care hospital
hypertension and hemorrhage. Severe maternal morbidity is
quantifiable and can be the best way of measuring the improvements in health care.15,16
In Mexico, 90% of maternal deaths occur in hospitals or
medical units. This is why the hospital MM rate is so high,
compared to the general population.17 In Nuevo Leon for
this period of time, the average MM rate was 9.9 per 100,000
born alive. When we compare our MM rate of 1.85 per 1,000
births with that from other hospitals, it is below the 2.46
and 2.48% reported by the Hospital Materno Perinatal del
Estado de México during 2007 and 200818 and by Peru (11.25
per 1,000 births).19 A common problem in concentration hospitals is the admittance of severe maternal complications,
which are referred very tardily. In our MM group we found
that 25 patients (67.5%), were referred in a bad condition.
The relation is as follows: of the hypertensive disorders, 12
out of the 14 fatal cases (85.7%) were referred to our hospital with brain hemorrhage; the 3 fatal cases resulting
from hemorrhage were treated in other hospitals and then
sent here; of the 6 fatal cases due to sepsis, 5 (83.3%) were
treated in other hospitals and then sent here; of the 13 fatal
cases from medical complications, 5 (19.2%) were admitted
to our department being very ill.
The pattern of the main obstetric causes of morbidity and
mortality has remained unchanged in the last decades;
however, the frequency of all the causes have risen. The 5
main causes worldwide are complications of abortion, postpartum hemorrhage, high blood pressure, antepartum hemorrhage and pre-existing medical conditions.20,21 The 407
SOM cases represent 2.03% of total births, i.e., 1 SOM case
for every 49 births. Obstetric morbidity and MM have a direct or close relationship. In our review, there were 37 maternal deaths and the 3 main reasons were: Hypertensive
disorders (37.8%), medical conditions (35.1%), and sepsis
(16.2%). In the same period of time, SOM incidence was as
follows: hypertensive disorders (76.1%, hemorrhage 14.2%,
and medical conditions 6.3%). There was only one difference in the hemorrhage cases: they occupied the second place
in obstetric morbidity, while they appear in 4th place as a
cause of maternal death with only 3 cases (Table 1).
When we applied the rates to all of the 5 groups of SOM
cases, a greater relationship with the severity of the illness
comparative with the number of cases (Table 4) was seen.
Therefore, among hypertensive diseases there was 1 death
for every 22 cases (4.5%) with hemorrhage, 1 for every 19.3
cases (5.1%) with medical complications and 1 death for
every 2 cases of sepsis (50%); there was also only 1 anesthetic complication which resulted in death (100%). These
results were positively correlated with the admittances to
NICU: 19.6% from hypertensive disorders, 4.9% hemorrhage,
92.3% medical conditions, and 66.6% sepsis.
The age group with the highest number of SOM were teenagers with almost 35%; 60% were single or in common-law
marriage. Eighty-two percent had finished junior high school
or higher (Table 5). Becoming pregnant at an early age
marks the beginning of long-term economic and social responsibilities, as most of these mothers have low income and
limited work options, favoring a vicious cycle of poverty.
This situation worsens with the inter-generational repetition of teenage pregnancy, increasing the risk of complications.22,23 Being single or living in common-law marriage
favors social exclusion and reduces economic expectations
23
as well as medical care for women.24 In our study all of the
patients were low income and did not have medical care
services.
Obstetric care in 354 reviewed cases was of 3 uterine curettages (0.84%), 38 deliveries (10.73%) and 313 C-sections
(88.41%). Historically, performing C-sections is related with
obstetric complications or associated with medical conditions.25
Conclusion
Assessment of MM in addition to SOM provides reliable data
about the prevalence of severe obstetric complications;
thus, this relevant information allows taking specific preventive measures as well as improving medical care and the
allocation of resources addressed at caring for women of
childbearing-age.26
Funding
References
1. Clasificación estadística internacional de enfermedades y problemas relacionados con la salud. Décima revisión. Publicación
científica 554. Organización Mundial de la Salud 1992;2:29-64.
2. Say L, Pattinson RC, Gulmezoglu AM. WHO systematic review of
maternal morbidity and mortality: the prevalence of severe
acute maternal morbidity (near miss). Reprod Health 2004;1:3–
7.
3. Pattinson RC, Buchmann E, Mantel G, et al. Can enquiries into
severe maternal morbidity act as a surrogate for maternal
death enquiries? Br J Obstet Gynaecol 2003;110:889–893.
4. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal
morbidity: A pilot study for a near miss. Br J Obstet Gynaecol
1998;105:985-990.
5. Prual A, Bouvier-Colle MH, de Bernis L, et al. Severe maternal
morbidity from direct obstetric causes in West Africa: Incidence
and case fatality rates. Bull World Health Organ 2000;78:593602.
6. Fitzpatrick C, Halligan A, McKenna P, et al. Near-miss maternal
mortality (Letter). Irish Med J 1992;85:37.
7. Baskett TF, Sternadel J. Maternal intensive care and near miss
mortality in obstetrics. Br J Obstet Gynaecol 1998;105:981-984.
8. de Bernis L, Dumont A, Bouillin D, et al. Maternal morbidity and
mortality in two different populations of Senegal: A prospective
study (MOMA Survey). BJOG 2000;107:68-74.
9. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal
morbidity: A pilot study for a near miss. Br J Obstet Gynaecol
1998;105:985-990.
10. Cabero Ll, Cerqueira Ma J. Protocolos de medicina materno-fetal (perinatología). 2da Ed. Barcelona: Ed. Ergon; 2000. p. 372.
11. Pattinson RC, Hall MH. Near misses: a useful adjunct to maternal death enquiries. Br Med Bul 2003;67:231-243.
12. Vandecruys HI, Pattinson RC, Macdonald AP, et al. Severe acute
maternal morbidity and mortality in the Pretoria Academic
Complex: changing patterns over 4 years. Eur J Obstet Gynecol
Reprod Biol 2002;102:6-10.
24
13. Fabre E, Carrera José M, Monleón J, et al. Cómo diseñar, realizar y comunicar la investigación clínica en perinatología. Depto. Obstetricia y Ginecología Instituto Universitario Dexeus.
Barcelona: Ed. Masson; 1998. p. 199-200.
14. Castañeda M. La mortalidad materna en México. Cuatro visiones críticas. Xochimilco, México: Fundar-UAM; 2004. p. 18.
15. Waterstone M, Bewley S, Wolfe Ch. Incidence and predictors of
severe morbidity: case control study. BMJ 2001;322:1089-1093.
16. Danel I, Berg C, Johnson Ch, et al. Magnitude of maternal morbidity during labor and delivery: United States, 1993-1997. Am
J Public Health 2003;93:631-634.
17. Instituto Nacional de Estadística y Geografía. Estadísticas de
defunciones, 2010. Base de datos. México: INEGI; 2011.
18. Briones JC, Díaz de León M, Meneses J. Estrategias para reducir
la mortalidad materna hospitalaria en el Estado de México. Rev
Asoc Mex Med Crit y Ter Int 2009;23:16-24.
19. Díaz J, Salvador JL, Hidalgo F. Mortalidad materna. Experiencia
de 4 años en el Hospital Nacional Cayetano Heredia. Ginecol
Obstet 2004;50:97-100.
20. Pattinson RC, MacDonald AP, Backer F, et al. Effect of audit on
critically ill pregnant women. Clin Govern Int J 2006;11:278288.
21. Brace V, Penney G, Hall M. Quantifying severe maternal morbidity: a Scottish Population Study. BJOG 2004;111:481-484.
22. Karam CM, Bustamante MP, Camarena GA. Aspectos sociales de
la mortalidad materna. Estudio de caso en el Estado de México.
Medicina Social 2007;2:205-211.
23. Alatorre RJ, Atkin CL. “El embarazo adolescente y la pobreza”,
en Paloma Bonfil y Vania Salles (eds.) Mujeres pobres: salud y
trabajo. México: Gimtrap; 1998. p. 13-30.
24. Lipman EL, Boyle MH. Social support and education groups for
single mothers: a randomized controlled trial of a communitybased program. CMAJ 2005;173:1451-1456.
25. Liu S, Liston RM, Joseph KS, et al. Maternal mortality and severe morbidity associated with low risk planned cesarean delivery
versus planned vaginal delivery at term. CMAJ 2007;176:455460.
26. Brace V, Penney G. Learning from adverse outcomes: A system
for identification and assessment of severe maternal morbidity.
Fetal Matern Med Rev 2007;18:121–144.
medicina
universitaria
www.elsevier.com.mx
Scientific letter
Sweet syndrome presenting late after non Hodgkin’s lymphoma
and dermatomyositis
L. A. Olguín-Ramíreza, J. C. Jaime-Péreza,*, C. Mendoza-Rodríguezb, D. GómezAlmaguera
Hematology Department, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital, School of
Medicine of the Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
a
b
Dermatology Department, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital, School of
Medicine of the Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: November 2013; Accepted: November 2013
KEYWORDS
Sweet syndrome;
Dermatomyositis;
Non-Hodgkin’s
lymphoma; Pulmonary
fibrosis; Mexico.
Abstract Sweet syndrome is a rare neutrophilic dermatosis consisting in the onset of high
fever, neutrophilia, and typical painful skin lesions including erythematous papules, nodules,
and plaques on the face, trunk, and extremities, with a bilateral and asymmetrical pattern.
Sweet syndrome is classified as idiopathic, predominating in women; malignancy-associated,
mainly with hematological cancer, and drug-induced.
The diagnosis is based on clinical history and skin manifestations, being confirmed by a complete blood count showing neutrophilic leukocytosis, and specific findings in the skin biopsy.
We report the case of a 68 year-old man with a 10-year evolution of dermatomyositis complicated by lung fibrosis, followed 8 years later by non-Hodgkin lymphoma (NHL) accompanied by
worsening of his fibrosis. Two years after the successful treatment of NHL the patient developed
an acute episode of severe dyspnea, multiple skin lesions, and 95% neutrophilia. At that time
the patient had a severe lung function impairment complicated by nosocomial pneumonia that
led to his death, a few days after the diagnosis of Sweet syndrome was established by histopathology examination.
Sweet syndrome is a rare dermatologic entity that can appear several years after diseases characterized by immune dysfunction such as dermatomyositis and NHL.
* Corresponding author: Hematology Departments, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital. Dr. Rodrigo Barragán Building, 2nd Floor. Madero y Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: +52 (81) 1257
2905. Fax: +52 (81) 1257 2906. E-mail address: [email protected] (J. C. Jaime-Pérez).
26
Introduction
Sweet syndrome was first described in 1964 by Robert Douglas Sweet.1 In 1986 Su and Liu postulated the criteria for its
diagnosis.2 There is no racial predilection, and it is more frequent in women (4:1).3-5
The disease consists of high fever, neutrophilia, and typical painful skin lesions including erythematous papules, nodules, and plaques on the face, trunk, and extremities, with
a bilateral and asymmetrical pattern.6,7
Sweet syndrome is classified as: a) idiopathic, which predominantly affects women between 30 and 50 years of
age;6,8 b) malignancy-associated, which appears to affect
men and women equally; in about 20% of the cases the syndrome is associated with a malignancy, most often acute
leukemia;9,10 c) drug-induced, which may occur as a reaction
to a medication, most frequently to granulocyte colony-stimulating factor (G-SCF).11-14
The diagnosis is confirmed by a complete blood count
(CBC) showing leukocytosis with a predominance of neutrophils, and a skin biopsy demonstrating edema of the papillary dermis and a dense inflammatory leukocyte infiltrate
in the lower dermis.5,6,15
The treatment includes prednisolone, or potassium iodide, colchicine, and Lugol’s solution.5,6,16 Usually recovery is
complete with no recurrence.
L. A. Olguín-Ramírez et al
coupled with the presence of disseminated macular dermatosis, which prompted a consultation to a dermatologist; at
that time the patient had painful erythematous papules
both over the dorsum of his forearm and face. The lesions
rapidly progressed to become nodules and a few of them
coalesced forming plaques (Fig. 1, panel C). A skin punch
biopsy performed on a left cheek lesion, demonstrated prominent infiltration of leucocytes into the dermis, consistent
with the diagnosis of sweet syndrome. (Fig. 1, panels D and
E). A CBC reported 10.9 x 109/l WBC, and neutrophilia of
10.3 x 109/l, representing 94.7% of total leukocytes.
During his stay at the hospital, the patient developed nosocomial pneumonia that progressed to respiratory failure,
and broad spectrum antibiotics were started; a CT scan
of the chest showed diffuse bilateral infiltrates, as well as
A
B
Case report
The patient, a 68-year-old man, first showed symptoms in
April 2000 with minimum effort dyspnea, accompanied by
constitutional symptoms and generalized myalgias with
weakness and muscular fatigue. At the time the CBC was
normal, but blood chemistry results showed diverse abnormalities including albumin 1.7 g/dl, globulin 4.1 g/dl, lactic
dehydrogenase 688 U/l, creatine kinase 7,402 U/l, alanine
aminotransferase 283 U/l and aspartate aminotransferase 521 U/l. Chest X-rays showed a bibasal reticular infiltrate
(Fig. 1, panel A). Computed tomography (CT) imaging documented interstitial fibrosis in the descamative phase. Spirometry reported a mild to moderate restrictive process.
Electromyography of the 4 extremities reported myopathic
inflammatory pattern. A muscle biopsy of the quadriceps
was normal. Diagnosis of dermatomyositis with secondary
lung fibrosis was established and treatment with prednisone
and methotrexate was started.
In 2008, physical examination revealed a 12 x 6 cm mass
of coalescent adenopathies, firm, nontender, fixed to deep
planes in the parotid gland, as well as cervical, retroauricular, bilateral axillary and inguinal lymphadenopathies; in
addition, the patient presented B symptoms; there was no
visceral enlargement. An excisional biopsy of the axillary
and left groin lymph nodes was carried out, leading to the
diagnosis of high-grade diffuse large cell non-Hodgkin lymphoma (NHL) with a B immunophenotype. Bone marrow
aspirate showed a moderate granulocytic hyperplasia (Fig.
1, panel B). Treatment included rituximab, cyclophosphamide, doxorubicin, and vincristine.
The patient had no major complications until November
2010, when he was admitted to the emergency room after 3
weeks of experiencing malaise, fatigue, and weakness,
C
D
E
Figure 1 A) The chest X-rays from 2008 (left) show a bibasal
reticular infiltrate; 2 years later on the last X-rays (right) diffuse bilateral infiltrates as well as significant progression of pulmonary fibrosis were documented. B) Bone marrow aspirate;
moderate granulocytic hyperplasia. C) Sweet syndrome. Sixtyeight male patient with disseminated dermatosis to the face,
predominating on the right supraorbital area and near the nasogenian ipsilateral furrow, characterized by ulcerated plaques
filled with necrotic central tissue and partly covered with crust,
surrounded by eritema, giving a targetoid appearance. D) Microscopic low-power magnification view of a hematoxylin and
eosin-stained skin punch biopsy performed on a left cheek lesion, demonstrating slight spongiosis and superficial erosions
scattered in the epidermis, with prominent dense infiltration of
leucocytes into the dermis. E) Microscopic high-power view demonstrating dense neutrophilic infiltration in the upper and
mid-dermis and neutrophil karyorrhexis.
Sweet syndrome presenting late after non Hodgkin’s lymphoma and dermatomyositis
significant progression of pulmonary fibrosis. The ventilatory function worsened, leading to a cardiorespiratory
arrest and death of the patient a week after his admission
to the hospital.
Discussion
Several theories to explain the pathogenesis of Sweet syndrome exist. 17 3 are widely supported a type III hypersensitivity reaction, an activation of T cells by antigens or
superantigens, and a disturbance in the function of the neutrophiles. An additional theory notes that inappropriate secretion of interleukin 1 (IL-1) can stimulate macrophages
and then cause a rise in the production of G-CSF, responsible
for increasing IL-8, a chemotactic factor for neutrophils.5,6
Confirming the knowledge about dermatomyositis in
that 10% to 25% of the cases progress to a malignancy,18,19
eight years after its diagnosis and successful therapy, the
patient developed NHL that was also successfully treated
and remained in remission.
Our patient presented three conditions associated with
the diagnosis of Sweet syndrome: an hematologic disorder, a
severe infectious process, and an autoimmune disease.20 In
this case it is difficult to establish definitively whether the
syndrome was associated to NHL or its therapy, as his dermatomyositis was not completely controlled, as shown by
progressive lung fibrosis and subsequent fatal pneumonia;
another possibility is that both conditions acted as a trigger
for the development of Sweet syndrome.
Funding
References
1. Anzalone CL, Cohen PR. Acute febrile neutrophilic dermatosis
(Sweet’s syndrome). Curr Opin Hematol 2013;20:26-35.
2. Su WP, Liu HN. Diagnostic criteria for Sweet’s syndrome. Cutis,
cutaneous medicine for the practitioner 1986;37:167-174.
27
3. Morita Y, Ogura T, Yamamura M, et al. Sweet’s syndrome associated with undifferentiated connective tissue syndrome. Ann
Rheum Dis 1995;54:937-938.
4. Mizoguchi M, Matsuki K, Mochizuki M, et al. Human leukocyte
antigen in Sweet’s syndrome and its relationship to Behcet’s
disease. Arch Dermatol 1988;124:1069-1073.
5. Gonzalez GE, Haro RR, Fariña MC, et al. Sindrome de Sweet en
la infancia. Piel 2008;23:118-124.
6. Cohen PR. Sweet’s syndrome--a comprehensive review of an
acute febrile neutrophilic dermatosis. Orphanet J Rare Dis
2007;2:34.
7. Boudysova M, Ettler K, Podhola M, et al. Acute febrile neutrophilic dermatosis - Sweet syndrome. Casopis lekaru ceskych
2012;151:359-361.
8. Knipstein JA, Ambruso DR. Sweet syndrome in an infant with
chronic granulomatous disease. J Pediatr Hematol Oncol
2012;34:372-374.
9. Hünermund A, Wendel AM, Geissinger E, et al. Typically atypical: histiocytoid Sweet syndrome associated with malignancy. J
Dtsch Dermatol Ges 2011;9:666-669.
10. Reina D, Cerdà D, Roig D, et al. Sweet syndrome associated
with myelodysplastic syndrome: Report of a case. Review of the
literature. Reumatol Clin 2013:9;246-247.
11. Kawakami T, Ohashi S, Kawa Y, et al. Elevated serum granulocyte colony-stimulating factor levels in patients with active phase
of Sweet syndrome and patients with active Behcet disease:
Implication in neutrophil apoptosis dysfunction. Arch Dermatol
2004;140:570-574.
12. Ginarte M, Toribio J. Sweet’s syndrome. Med Clin (Barc)
2009;133:31-35.
13. Akpinar F, Dervis E. Drug eruptions: An 8-year study including
106 inpatients at a dermatology clinic in turkey. Indian J Dermatol 2012;57:194-198.
14. Trickett HB, Cumpston A, Craig M. Azacitidine-associated
Sweet’s syndrome. Am J Health Syst Pharm 2012;69:869-871.
15. Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: Pyoderma gangrenosum and Sweet’s syndrome. Postgrad Med J
1997;73:65-68.
16. Schadt CR, Callen JP. Management of neutrophilic dermatoses.
Dermatologic Therapy 2012;25:158-172.
17. Martinez Martinez ML, Cordoba Soriano JG, Rodriguez Vazquez
M, et al. Sweet syndrome. Med Clin (Barc) 2012;139:e7.
18. Owen CE, Malone JC, Callen JP. Sweet-like dermatosis in 2 patients with clinical features of dermatomyositis and underlying
autoimmune disease. Arch Dermatol 2008;144:1486-1490.
19. Pelosof LC, Gerber DE. Paraneoplastic syndromes: An approach
to diagnosis and treatment. Mayo Clin Proc 2010;85:838-854.
20. Saffie M, Sun D, Hsia C. Sweet’s syndrome in chronic myelomonocytic leukemia. American Journal of Hematology
2013;88:630.
medicina
universitaria
www.elsevier.com.mx
REVIEW ARTICLE
Mild cognitive impairment
J. Isordia-Martíneza,*, F. Gongora-Riverab, H. Leal-Baileyb, X. Ortiz-Jiménezc
Department of Internal Medicine, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo
León, Monterrey, N. L., Mexico
a
Service of Neurology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey,
N. L., Mexico
b
c
Laboratory of Psychophysiology, Faculty of Psychology, Universidad Autónoma de Nuevo León, Monterrey, N.L. Mexico
Received: May 2013; Accepted: December 2013
KEYWORDS
Mild cognitive
impairment;
Dementia; Cognitive
function; Mexico.
Abstract Mild Cognitive Impairment (MCI) is a disease between normal cognitive ageing and
dementia. In recent years the term MCI has been recognized as a pre-dementia state, raising an
important subject for investigation in the prevention of dementia. There are various terms
related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer’s disease;
most of them do not comprise all the areas related to MCI. A central cholinergic deficit is
present in amnestic MCI with neuronal loss in the Meynert basal nucleus. It is estimated that the
rate of progression to dementia is about 10% every year. The prevalence of MCI is 10%-11% and
the risk of progression to dementia is about 5%-16%. The continual development of pharmacologic
approaches to modify and delay the natural history of progression of the disease motivates a
great interest in an earlier diagnosis.
Introduction
Mild cognitive impairment (MCI) is an intermediate mental
state between a normal cognitive state and dementia. In
recent years, MCI has been recognized as a pre-dementia
state, becoming an important subject for investigation in
the prevention of dementia. There are several terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer disease (AD); most of them do not
comprise all the area related to MCI.1 MCI is a heterogeneous pathology in terms of clinical presentation, etiology,
prognosis and prevalence; however, there is still controversy in its definition. Some studies have demonstrated that
MCI can be reversed to a normal cognitive state. Prevalence
is 3-19% in the elderly population, with an incidence between 8 to 58 per 1,000 people a year and a risk of developing into dementia of 11-33% within 2 years. 2 Memory
disorders represent a public health issue, with an average of
4.5 years until a patient is diagnosed with dementia, with
major disabilities and economic loss for the family and the
health sector.3,4 In Mexico there is no information about patients’ survival.
* Corresponding author: Madero y Gonzalitos Avenue, Z.P. 64700, Monterrey, N. L., Mexico. Telephone/Fax: (81) 8333 7798. E-mail address:
[email protected] (J. Isordia-Martínez).
Mild cognitive impairment subgroups
Amnestic MCI
It is considered to be AD’s main predecessor; it is the most
common subgroup with a 2:1 ratio compared with non-amnestic MCI. There are 2 classifications within this subgroup:
single non-memory domain MCI and multi-domain MCI. The
former refers to individuals who have a significant memory
deficit (classified by the result of a battery of neuropsychological tests) but do not meet the criteria for a dementia
diagnosis; criteria for this classification are: presence of a
cognitive complaint (confirmed by an informant), impaired
memory determined objectively (correlated with age and
educational level, and represented by an impairment greater than 1.5 standard deviations [SD] from the normal parameter), preserved general cognitive functions, the fact that
everyday activities remain normal, and not meeting criteria
for a dementia diagnosis. Amnestic multi-domain MCI includes those people who do not manifest a cognitive decline
greater than 0.5-1 SD for their age and educational level.
We have followed up on these patients and they generally
do not display an evolution towards vascular dementia or
AD.5
Within this MCI subgroup, the cognitive profile reflects
normal aging; prognostic usefulness of this MCI is not clear.
There is controversy among the different studies regarding
this subgroup’s conversion to dementia or the return to a
normal cognitive state.6
Non-amnestic MCI
This type of MCI is characterized by an isolated impairment in
a single non-memory domain, for instance an impairment of
the executive function, language, or visuospatial skills. The
non-amnestic MCI-single domain subgroup will progress, depending on the affected domain, to fronto-temporal
dementia, primary progressive aphasia, Lewy body dementia, progressive supranuclear palsy, or corticobasal degeneration. Individuals in this group are considered to have a
lower risk of conversion to dementia; however, evidence
supporting this theory is limited. In regard to the non-amnestic multiple domains MCI subtype, it is considered that
one of the main disorders is the development of neurofibrillary plaques caused by the proteins tau and alfa-synuclein.7
Epidemiology
There is a great variation between the reported prevalence
rates, fluctuating between 2% and 20% in different series.
Studies which have used different measurements such as
age-related cognitive decline, cognitive impairment, no dementia, and minimal dementia estimate prevalence between 16% and 22% in adults older than 60. In several
cohort-type studies, incidences between 14 and 77 for every
1,000 patients older than 60 years have been reported. Males have an odds ratio of 1:5 in community studies of patients between 70 and 89 years.2 The National Health and
Aging Study in Mexico (ENASEM by its Spanish acronym) assessed the prevalence of cognitive impairment and its relationship with sociodemographic factors in the population,
29
finding that just 7% had cognitive impairment and 3.3% had
cognitive impairment and functional dependency.3
Pathology
Regarding histopathological findings, and MCI being a clinical
expression of early symptoms of dementia, researchers detected intermediate findings between normality and advanced
dementia. A central cholinergic deficit is present in amnestic
MCI, related to neuronal loss in the basal nucleus of Meynert.8
In postmortem studies, evidence of a positive regulation in
the acetyl transferase activity in the frontal cortex and hippocampus has been found.9 There is evidence that cerebrovascular and neurodegenerative conditions contribute to MCI,
especially white matter lesions and small lacunar infarcts.10
One of the main problems in the diagnosis of MCI is determining how much the memory processes are affected. Some
criteria establish that in order to reach a diagnosis of MCI,
the patient’s performance carrying out memory tasks must
be inferior to the average obtained by normal adults; however, other criteria establish that for a diagnosis of MCI, patients must be compared with subjects of the same age and
educational level.
A very important point in the subgroup of patients with
diabetes mellitus is to recognize that there is an exacerbated neurotoxicity caused by the beta amyloid plaques secondary to the advanced glycation end-products in their
matrix; moreover, in animal models the existence of a diminished cholinergic transporter in patients with cognitive impairment and diabetes has been found4 (Fig. 1).
Hypertension has been studied as a risk factor for cognitive impairment because it affects cerebral vasculature
through different mechanisms, including strokes, leukoaraiosis, atherosclerosis, etc.
In transversal studies, it has not been possible to find an
evident association with arterial hypertension as a risk factor while in longitudinal studies such association has been
demonstrated. Dyslipidemia has also been studied in different population samples finding a correlation between MCI
and hyperlipidemia (especially hypercholesterolemia)
in middle-aged patients. Furthermore, we are able to see in
different studies that there is a protective association between the use of statins and MCI. Other risk factors which
have been analyzed include chronic renal failure, vitamin
B12 deficiency, vitamin D deficiency, hyperhomocysteinemia, testosterone deficiency, subclinical hypothyroidism,
smoking, and excessive alcohol consumption.
Population studies
Many authors and institutions (The World Health Organization and The American Academy of Neurology, among
others) have supported the term MCI. In recent years they
have been trying to establish a greater delimitation of the
term, mainly because different types of mild cognitive impairments have arisen (amnestic, non-amnestic, aphasia,
apraxia or agnostic).
Most of the studies are directed at evaluating MCI, and
are focused, mainly, in observing the performance in the
memory processes in older people, considering there is
well-founded evidence showing that cognitive complaints
30
J. Isordia-Martínez et al
OVERPRODUCTION
AND DECREASE
OF AMYLOID-BETA
PURIFICATION
PRECLINICAL STAGE
BETA-AMYLOID
ACCUMULATION
MCI
ACTIVATION OF
NEUROTOXIC
CASCADES
BETA-AMYLOID
OLIGOMERS
HYPERPHOSPHORY
LATION OF THE
TAU PROTEIN
GLIAL INFLAMMATION,
OXIDATIVE STRESS,
MITOCHONDRIAL
DYSFUNCTION
AMYLOID
PLAQUES
SYMPATHETIC
AND AXONAL
DYSFUNCTION
NEURITIC
PLAQUES
NEUROFIBRILLARY
PLAQUES
DEMENTIA
DEMENTIA
Figure 1 Histopathologic changes in the brain and its clinical correlation.
have a high prevalence in this population, suggesting a preclinical phase of a process of dementia; even though there
are many longitudinal cohort studies of non-demented subjects, who have been developing cognitive impairment.
One of the most representative investigations about MCI,
and one which has been taken as a reference, was carried
out by the researchers at Mayo Clinic in the United States.
The objective of the researchers was to clinically classify
subjects with MCI through a transversal and longitudinal study. A sample of 76 subjects with MCI was compared to 234
control subjects and with 106 patients with mild AD from
the clinic or from the community register of patients with
AD in Rochester. All 3 groups were evaluated longitudinally
using instruments which evaluate cognitive performance
(MMSE, WAIS-R, WMS-R, Dementia Rating Scale, Free and
Cued Selective Reminding Test and Rey’s Auditory Verbal
Learning Test, among others). Mild AD diagnosis was established by the DSM-III-R and the NINCDS-ADRDA. The results
showed that in general intelligence measurements, subjects
with MCI performance were more similar to that from control subjects than from patients with mild AD. In particular,
in the complete WAIS-R scale, control subjects obtained an
average IQ = 101.8 and subjects with MCI obtained an average IQ = 98, while patients with mild AD obtained an average
IQ = 83.9. The results with the MMSE were very similar; control and MCI subjects obtained an average score of 28.3 and
26 respectively, while patients with mild AD obtained an
average score of 22.6. On the other hand, subjects with MCI
obtained a lower result than control subjects in the Controlled Oral Word Association Test, even though these results
were within the normal expected range for their age, based
on the community studies used for this research. However,
performance carrying out memory tasks was very similar in
subjects with MCI and patients with mild AD, yet the declining range of subjects with MCI performing these kinds of
tasks was lower to the one showed by patients with mild AD
but higher than that in control subjects. Researchers came
to the conclusion that subjects considered under MCI criteria may be differentiated both from control subjects and
patients with mild AD, thus considering MCI as a clinical entity characterized by a group of symptoms and amenable to
of pharmacologically interactive treatment.5
Another study with great significance in MCI research was
one carried out in St. Luis Missouri, US, where the local elderly population volunteered. The sample was of 454 subjects, who were classified according to the CDR as
“cognitively healthy” (n = 177 y CDR = 0) and Lewy body
dementia (LBD) (n = 277 and CDR = 0.5).
Based on the clinical suspicion that MCI represents an
early stage of Alzheimer’s, the MCI group with a score on the
CDR = 0.5 was subdivided into three subgroups. The study
had a follow-up of 9-and-a-half years, evaluating subjects
with a neuropsychological battery and a neuropathological
test for the subjects who passed away during research.
The objective was to observe the progression of subjects towards a score in the CDR = 1, which characterizes
“definite” mild Alzheimer’s. The evaluation protocol included items from brief standardized cognitive assessment batteries, such as MMSE and the Short Blessed Test (Katzman
et al. 1983), among others. In general, the results showed
that all the subjects with CDR = 0-5 displayed memory impairment and a higher frequency of alelo e4 of the gene
apoe compared to normal subjects CDR = 0. The second cognitive domain frequently more impaired was the judgment
and problem solving skill. On the other hand, the results
showed that 100% of the subjects of the group CDR=5Alzheimer’s progress to a severe dementia in a period of 9.5
years, of the rate of conversion of this group to Alzheimer’s
in 5 years 60.5% with an equal or superior score to 1 in the
CDR. In the CDR = 0.5- incipient Alzheimer’s, the range
of conversion to Alzheimer’s in 5 years was 35.7% and, for
the CDR = 0.5- uncertain dementia, its range of conversion
in the same period of time was 19.9%; However, in the control subjects (CDR = 0), the conversion range was only 6.8%.
The conclusion was that MCI generally represents an early
stage of Alzheimer’s, due to the fact that progression to a
severe dementia correlates with the base line of the degree
of impairment, in other words, 96% of the subjects with CDR
= 0.5 progressed to a neuropathological state of dementia,
and out of these, 84% were an Alzheimer-type dementia1
In a different study, Ritchie et al, with the objective of
evaluating the predictive validity and temporal stability
of the diagnosis criteria of MCI, analyzed a sample of 833
subjects with subclinical cognitive impairments, taken from
a previous longitudinal study called the Eugeria Project, carried out in Montpellier, in the south of France. The sample
was representative of the population and covered urban as
well as rural populations. The study followed the cohort
of subjects during a period of 3 years. During the first year,
subjects were evaluated with an instrument used to screen
cognitive functioning denominated Détérioration Cognitive
Observée (DECO), which has demonstrated in diverse studies its high sensitivity to detect early changes in cognitive
functioning due to different causes, observing the degree of
change during the last year. Its estimation is similar to the
one of a close person who has had continuous monthly contact with the patient during a period of three years. Using a
neuropsychological computerized exam which covers most
of the cognitive functions, six cognitive domains were selected; attention, primary memory, secondary memory, visuospacial skills, language and reasoning. In a second phase,
MCI subjects were classified. The results showed that MCI
prevalence in the general population was approximately
3.2%, and of cognitive impairment adjusted to their age of
19.3%. Thus, MCI turned out to be a poor background to
a preclinical dementia phase in a period of three years, with
a risk of conversion of 11.1% constituting, in general, an
unstable group, because most of the subjects who belonged
to this group, experimented category switches every year.
On the contrary, the cognitive impairment adjusted group
proved to be more homogenous and stable, with a conversion rate to dementia of 28.6% in a period of 3 years. The
researchers came to the conclusion that criteria for MCI provide a poor performance when applied to a representative
sample, given the fact that in most of the investigations
which proposes MCI as a clinical diagnostic entity, samples
have been obtained out of small selected clinical groups.
Because cognitive complaints in older adults are the main
31
symptom to establish MCI criteria, several clinical studies
have been carried out. These studies have tried to establish
the predictive power of cognitive complaints in the memory
processes.6 Furthermore, it is important to emphasize “The
Canadian Study of Health and Aging” for its importance in
which they carried out a 5-year follow-up of 10,263 elderlies (over 65 years and up), representing the general population of older adults (residents of the community, as well
as institutionalized). In this epidemiologic study about
health care, dementia and functional state the term “nodementia cognitive impairment” surfaces, which represents
a cognitive disorder accompanied by a mild neuro-cognitive
disorder, also, it is attributable to a subjacent functional disorder. In this study they obtained results which indicate
that non-dementia cognitive impairment prevalence is
16.8% in people older than 64 years. From this study on,
several parallel studies utilized samples from this study7
(Fig. 2).
Clinical assessment
The corner stone of diagnosis consists of a detailed clinical
interview, ideally with the presence of an informant. There
are several scale systems, since 1982 there have been 2
main ones which are used to this day: Clinical Dementia Rating (CDR) which gives a point system of 0 for normal
people, 1 for mild dementia, and 0.5 for mild cognitive deterioration, and The Global Deterioration Scale (GDS) which
scores mild cognitive deterioration with a score of 3 where
patients display cognitive deficits and suffer alterations in
the executive function which affects social and occupational activities. It is important to keep in mind that the scales
do not mean 100% MCI diagnosis, because it is necessary to
check it with the clinical findings, and medical history. In
order to evaluate the subjects’ cognitive profile using the
Folstein Mini-Mental State Examination Tool (MMSE), or via
Montreal Cognitive Assessment (MOCA) taking into account
their respective sensitivity and specificity. A medical and
neurological examination must be carried out in order to
identify non-degenerative cognitive alterations causes8,9
(Fig. 3).
Emphasizing MMSE is one of the most utilized tests to evaluate these cognoscitive symptoms, it is very important to
remember that this test assesses memory, orientation, language, spatial skills, attention, and calculus. It takes about
10 minutes to apply. Its score ranges from 0 to 30. A cut-off
PERFORMANCE
COGNITIVE
NORMAL
AGING
FUNCTIONAL
MILD
COGNITIVE
IMPAIRMENT
Figure 2 Dementia spectrum.
DEMENTIA
32
point of 23 is generally recommended as an indicator of
cognitive impairment. The test has a reliability of 0.89. One
of its limitations is the fact that it is influenced by several
factors; for example, the level of education. Some authors
even consider the test to be affected by the patient’s ability
to read. Other authors believe the test is affected by demographic factors such as gender and age. Therefore, differential cut-off points between subgroups have been suggested
and alternative items have been generated (Galasko: the
months of the year backwards).
There are certain considerations which must be taken into
account for MCI diagnosis:
1. An international working group has formulated specific recommendations in MCI criteria: The individual is not demented nor fits in the normal category. There should be evidence of impairment in
cognition, demonstrated by a decline in time, or
subjective reports made by an informant. Everyday
activities are preserved and complex functions are
intact or minimally affected.10
2. It has been noted that neuropsychiatric symptoms
including dysphoria, irritability, hallucinations,
apathy, depression, agitation, and delusions are
more frequent in MCI and Alzheimer dementia patients. The presence of neuropsychiatric symptoms
involves a greater risk for MCI patients of progressing into AD. The Neuropsychiatric Inventory (Cummings et al., 1994) is the most used scale to assess
neuropsychiatric alterations including 12 areas (agitation, delusion, hallucinations, depression, euphoria, abnormal motor activity, apathy, irritability, disinhibition, anxiety, drowsiness and hunger); a
patient’s relative who may have the information is
questioned about these symptoms.11
CLINICAL
DEGENERATIVE
CLASSIFICATION
AMNESTIC
MCI
NONAMNESTIC
MCI
3. Psychiatric conditions (depression), medication adverse events (anticholinergics, antihistamines),
sleep disorders, infections, metabolic diseases (vitamin B12 deficiency, hypothyroidism, hyperglycemia, hypoglycemia, uremia, hepatopathy, sodium
disorders), structural brain diseases.11 Due to a
great diversity of pathologies, researchers have
tried to find ideal biomarkers for a more accurate diagnosis; we must remember that markers may
be positive in non-demented subjects. Some of
these markers reflect key cognitive impairment
processes in the cerebrospinal fluid, such as the levels of isoform of beta 42 amyloid and Tau protein.
Other studied markers include amyloid deposits or
neurofibrillary plaques like Pittsburgh B compound
or the 18-FDDNP.12 There are other markers which
reflect secondary processes like neuron dysfunction
or neuronal loss either by electroencephalogram
(EEG), nuclear magnetic resonance or positron
emission tomography scan. As far as EEG goes, researchers have found that the rate between theta
and alpha 1 waves is a reliable individual rate of
cerebrovascular damage.13
4. Cerebral biopsy plays a very limited role in the
diagnosis of dementia; its diagnostic capabilities
are minimal, the procedure is invasive and involves risk for major complications. The biopsy is reserved for younger patients and for those with atypical clinical presentations with potentially
treatable causes.
It is very important to promote the recognition and acknowledgement of this pathology as several studies have
shown that between 29% and 76% of the cases may be identified in first contact care.14 Studies show that patients with
SINGLE
DOMAIN
ALZHEIMER
DISEASE
MULTIPLE
DOMAINS
ALZHEIMER
DISEASE
SINGLE
DOMAIN
FRONTOTEMPORAL
DEMENTIA
MULTIPLE
DOMAINS
LEWY BODY
DEMENTIA
Figure 3 Clinical classification and cause of MCI.
VASCULAR
PSYCHIATRIC
DEPRESSION
VASCULAR
DEMENTIA
VASCULAR
DEMENTIA
DEPRESSION
33
MCI display a wide range of malnutrition. A study by The
European Society for Clinical Nutrition and Metabolism
found that from a sample of 623 patients, 18% had a normal
nutrition status, 58% were at risk of malnutrition, and 24%
showed clear malnutrition; thus, we must keep in mind that
these types of patients display more alterations within the
corporal economy in addition to neurological deficiencies.15
Within a pragmatic approach in the study of MCI, it is of
great importance to cite several key questions for a proper
assessment16 (Fig. 4):
1. What is the patient’s basal functional status?
2. How is the symptomatology’s evolution? (regarding
time of onset)
3. What is the main characteristic of this deficit?
(short-term or long term memory)
SUBJECTIVE
MEMORY
COMPLAINT
NORMAL
COGNITIVE
FUNCTION
NORMAL AGING
SIGNIFICANT
FUNCTIONAL
DISABILITY
DEMENTIA
INCOMPLETE
COGNITIVE
IMPAIRMENT
NORMAL
DEPRESSION
AGING
ALZHEIMER
DISEASE
Figure 4 Clinical approach to MCI.
Neuroimaging
Neuroimaging use is controversial; most guides do not recommend routine imaging studies, but they include rules to
help identify patients who may have reversible causes of
dementia, with factors that include being under 60 years
old, showing focal neurological signs, and having been
affected less than 2 years from the onset of the disease.
However, their sensitivity and specificity are low. Magnetic
resonance imaging (MRI) findings include focal and generalized atrophy, as well as white matter lesions; in general,
these are unspecified findings. A tomography is important
in those patients with acute unsaturation of the cognoscitive impairment and rapid neurological deterioration.17
A longitudinal cohort study was carried out in Rotterdam,
The Netherlands. The main objective of this study was to
determine whether or not the hippocampus and amygdala
volume measured by MRI were useful for predicting the development of dementia in older people without cognitive
impairment. The investigators monitored 511 patients between 60 and 90 years of age, for an average period of 6
years. Over this period of time, the atrophy of the hippocampus and the amygdala measured by MRI predicted a
time of development of dementia of 6 years, with a risk rate
adjusted to age, gender, and educational level of 3 (95%
confidence interval [CI] 2.0-4.6) for every unit of standard
deviation for the hippocampus and of 2.1 (95% CI 1.5-2.9)
for the amygdalin level. In patients with cerebral atrophy
and leukoaraisis, the exact correlation degree and influence
between imaging findings and the results of the neuropsychological tests are unknown. Therefore, it is hard to classify this type of patient, because there are cases with major
pathological findings and imaging representing a preserved
cognition.18
Transcranial Doppler ultrasound
PROMINENT
MEMORY
DISABILITY
AMNESTIC MILD
COGNITIVE
IMPAIRMENT
4. Are there any changes in behavior?
5. Is there a co-existence of depression in this patient?
6. Could the patient in question have a serious subclinical pathology?
Imaging techniques to analyze cerebral circulation are very
diverse, there is no such thing as the ideal study. Transcranial Doppler ultrasound is a test performed with a portable
device which allows measuring several blood flow parameters as well as the Circle of Willis, providing information
about the velocity of blood flow (cm/s) through the brain’s
blood vessels, resistance rates, and pulsatility, as well as
the brain’s vasoreactivity following stimuli such as hyperventilation, induced hypercapnia, and even medications
like acetazolamide. This study is performed with the patient in a decubitus position, after resting for 10 minutes, at
room temperature, and comfortable, with the head at a 30
degree angle in a semi-Fowler position; a basal register is
recorded and blood pressure registered every 5 minutes
during the inhalation of 5%-7% carbon dioxide (CO2) for 5
minutes with an aesthetic mask covering both mouth and
nose. The most utilized protocol is to register the velocity
of systolic and diastolic flow, as well as the average resting
34
flow of the middle cerebral artery and then again 5 minutes
after inhaling CO2, assessing the responsive ability of cerebral arteries on entrance of carbon dioxide, numbers that
adjust to age, gender, and changes in blood pressure. In patients with hypertension, after the vasodilator stimulus there is a decrease in the cerebral microvascular reactivity
(explained by the decrease in the dilation ability to the vasodilator stimulus), which can be improved through the administration of antihypertensive medications.19
It has been shown that cerebral blood flow and cerebral
vasoreactivity gradually decrease with age, and that this
decrease is directly related to the presence of cerebral micro-strokes and impairment of cognitive function; in addition, vasoreactivity of the occipital is diminished even more
in vascular dementia which is statistically significant compared to AD.20
is a scale with 6 categories, and is based in orientation,
judgment, memory, personal care, performance within the
house and hobbies, with a score of over 1, a specificity of
94% was demonstrated and a sensitivity of 92%.
Diabetic patients have an odds ratio of 1.2-1.5 to obtain
lower scores than those who are non-diabetics, regarding
cognitive function; measured by Mini-Mental and the digital
symbol test.22
An adequate conversion to dementia prediction must be
made on those patients with mild cognitive impairment already established, there are several models; one of the
most important is the “Five-Predictor Combination” with a
sensitivity of 85.2% and 90% specificity based on age, MiniMental result, “Selective Reminding Test”, Functional activities questionnaire and University of Pennsylvania smell
identification test23 (Fig. 5).
Progression to dementia
Importance of the subject
The risk of dementia progression is estimated to be 10% per
year; as for MCI patients, yearly progression rates fluctuate
between 5% and 16%. Several long-term studies (over 5
years) have found that the risk of conversion decreases with
time. Some of the factors associated with an increased risk
of progression to dementia are socioeconomic variables and
age while gender and level of education are not considered
as factors. Age constitutes the main predictor of progression, risk increasing exponentially for every year people get
older. The apolipoprotein E-epsilon4 (APOe4) genotype has
been associated with an increased risk, as well as raised levels of the protein Thr phosphorylated tau 181, low levels of
amyloid beta 42, rise in the activity of the beta-secretase,
and of neprilysin (a degrading enzyme beta-amyloid peptide) activity diminution. An important rate of reversion of
MCI to a normal cognitive state is observed (20%-25%).21
The American Academy of Neurology’s evidence–based
guidelines for early detection states that MCI patients
should be detected early and followed long-term, because
of their high risk of subsequent development of dementia.2
For dementia detection in individuals suspected of cognoscitive impairment, screening instruments used to assess
progression are: Mini-Mental State Examination (score of
224 or less, specificity 57%-99%, sensitivity 82%-99%, positive predictive value 68%-91%, negative predictive value 96%99%, evidence class I and II, the percentages vary because
of the risk of dementia in each population, age classification, etc.), Kokmen short test of mental state (specificity
88%, sensitivity 86%), 7-minute screen, memory impairment
screen (specificity 96%, sensitivity 87%, positive predictive
value 54%-85%), Clock drawing test (specificity 96%, sensibility 92%), and Blessed dementia rating scale (specificity
46%, sensitivity 94%).
Moreover, different instruments should be applied for different aspects of the cognoscitive function, being more
useful the ones which emphasize memory, for example the
Mattis dementia rating scale (mainly focused on attention,
initiative, perseverance, building, memory, and conceptualization, between 129/144, sensitivity 98%, specificity 97%).
It is necessary to apply neuropsychological batteries on
the risk population, like the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) or the CDR which
The constant emergence of pharmacological and non-pharmacological preventive treatments to slow down or modify
the course in AD and the other types of dementia, boost a
great interest of reaching an early diagnosis in order to start
acting as soon as possible with these patients. MCI is an adequate state for new therapies, thus its differential diagnosis
is crucial, and a thing that nowadays is controversial, with
great debates regarding its delimitation and acceptance as
a new diagnostic entity. The development of specific instruments for MCI diagnosis is one of the most urgent tasks, given the fact that the current instruments have a significant
tendency to only detect risk factors. Different studies agree
that an adherence to the Mediterranean-style diet (hazard
ratio [HR] = 0.60, CI 0.42-0.87) and high physical activity
(HR = 0.67, CI 0.47-0.95) are independently associated with
a reduced risk of cognitive impairment.24 Knowledge of an
adequate control of systemic hypertension reduces the risk
of developing vascular dementia, dementia with Lewy bodies, and frontotemporal dementia; nevertheless, it does
not significantly decrease the development of MCI (RR =
0.97, CI 0.92-1.03) or AD.25 Currently, there is little evidence of the effectiveness and specificity of interventions that
ALZHERIMER´S
DISEASE
AMNESIC MCI
AMNESIC
VASCULAR
DEMENTIA
MULTIPLE
DOMAIN MCI
NOT AMNESIC
LEWY BODY
DEMENTIA
FRONTAL
TEMPORAL
DEMENTIA
NON-AMNESIC
MCI
PSYCHIATRIC
DISORDERS
Figure 5 Progression of mild cognitive impairment.
improve memory in the healthy elderly and those with MCI;
studies show that after a systemic training the results improved in immediate and delayed verbal memory. Information
to recommend MCI screening in asymptomatic individuals is
lacking. Therefore, there is ongoing research and population
analysis in order to determine which subjects will benefit
the most from the search of this pathology.26
Treatment
Adherence to a Mediterranean-style diet has been marginally associated with the reduction of progression of MCI to AD
(HR = 0.55, 95% CI 0.34-0.9).27
According to the Cochrane Collaboration, there are no
studies assessing the role that carbohydrates play in improving the performance of the evaluation in older people with
MCI.28
High-intensity aerobic exercise may be beneficial for patients with MCI; results of studies carried out with small randomized samples to exercise 40 to 60 minutes 4 days a week
for a period of 6 months, have shown that exercise improved the levels of the factor similar to the growth hormone,
plasma insulin reduction when fasting, cortisol, and executive function.29
Cholinesterase inhibitors slow down the conversion to full
dementia for up to 3 years, but it has been associated with
adverse effects in adults with MCI (diarrhea, nausea, vomiting, cramps, insomnia, headaches, syncope or vertigo); the
most studied are donepezil, galantamine, and rivastigmine,
the relative risks of progression to dementia are 0.69 (95%
CI 0.47-1) within 1 year, 0.67 (95% CI 0.55-0.83) within 2
years, and 0.84 (95% CI 0.7-1.02) within 3 years.30which is
frequently updated from the major healthcare databases
(MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs
Galantamine is not recommended because of the mortality risk increase, with a number needed to harm (NNH) of
100;31 in addition, it has not really been associated with a
diminution in the progression to dementia.32
In regards to donepezil, it may slow down the progression
of AD; this is based on randomized studies of patients who
received this medication at 5 mg a day for 6 weeks, which
was titrated to 10 mg a day for 3 years. In general, the progression to dementia was seen in 16% of the 769 patients,
with a significant improvement at 6, 12 and 24 months;
among patients who were carriers of APOe4, the improvement in executive function was notable up to 3 years of follow-up.33 The most common adverse effects were diarrhea
(NNH 10), cramps (NNH 7), insomnia (NNH 11), nausea
(8.4%), vomiting (6%), and arthritis (2.5%).34
There are other diverse therapies for which the net clinical benefit provided is unknown; these include nicotine
patch,35 gingko biloba,36 vitamin E,11 vitamins B637 and B12,38
folic acid,39 procaine,40 piracetam,41 and huperzine A.42
Funding
35
Acknowledgement
Our acknowledgement and appreciation to the Neurology
Services of “Dr. José Eleuterio González” University Hospital, particularly to Dr. Hector Jorge Villarreal, for all the
facilities provided.
References
1. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild
cognitive impairment. Arch Neurol 2001;58:1985–1992.
2. Panza F, D’Introno A, Colacicco AM, et al. Current epidemiology
of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 2005;13:633–644.
3. Mejía AS, Miguel JA, Villa A, et al. Deterioro cognoscitivo y factores asociados en adultos mayores en México. Salud Publica
Mex 2007;49:s475–s481.
4. Pasquier F, Boulogne A, Leys D, et al. Diabetes mellitus and dementia. Diabetes Metab 2006;32:403–414.
5. Petersen RC, Smith GE, Waring SC, et al. Aging, memory, and
mild cognitive impairment. International Psychogeriatrics
1997;9:65-69.
6. Artero S, Touchon J, Ritchie K. Disability and mild cognitive impairment: a longitudinal population-based study. Int J Geriatr
Psychiatry 2001;16:1092–1097.
7. The Canadian Study of Health and Aging: risk factors for
Alzheimer’s disease in Canada. Neurology 1994;44:2073–2080.
8. Rosenberg PB, Johnston D, Lyketsos CG. A clinical approach to
mild cognitive impairment. Am J Psychiatry 2006;163:1884–
1890.
9. Kelley RE, Minagar A. Memory complaints and dementia. Med
Clin North Am 2009;93:389–406.
10. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of
the International Working Group on Mild Cognitive Impairment.
J Intern Med 2004;256:240–246.
11. Burns A, Iliffe S. Dementia. BMJ 2009;338:b75–b75.
12. Visser PJ. Use of biomarkers to select the target population for
clinical trials in subjects with mild cognitive impairment. Journal of Nutrition, Health & Aging 2009;13:344-345.
13. Moretti DV, Miniussi C, Frisoni G, et al. Vascular damage and
EEG markers in subjects with mild cognitive impairment. Clin
Neurophysiol 2007;118:1866–1876.
14. Holsinger T, Deveau J, Boustani M, et al. Does this patient have
dementia? JAMA 2007;297:2391–2404.
15. Orsitto G, Fulvio F, Tria D, et al. Nutritional status in hospitalized elderly patients with mild cognitive impairment. Clin Nutr
2009;28:100–102.
16. Young J, Meagher D, Maclullich A. Cognitive assessment of older
people. BMJ 2011;343:5042–5042.
17. Oppenheim C, Naggara O, Frédy D, et al. Démences : place de
l’imagerie. Journel Radiologie 2003;84:1819–1828.
18. Podemski R, Pokryszko-Dragan A, Zagrajek M, et al. Mild cognitive impairment and event-related potentials in patients with
cerebral atrophy and leukoaraiosis. Neurol Sci 2008;29:411–
416.
19. Settakis G, Páll D, Molnár C, et al. Cerebrovascular reactivity in
hypertensive and healthy adolescents: TCD with vasodilatory
challenge. J Neuroimaging 2003;13:106–112.
20. Asil T, Uzuner N. Differentiation of vascular dementia and
Alzheimer disease: a functional transcranial Doppler ultrasonographic study. J Ultrasound Med 2005;24:1065–1070.
21. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline
and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia 2005;48:2460–
2469.
36
22. Devanand DP, Liu X, Tabert MH, et al. Combining early markers
strongly predicts conversion from mild cognitive impairment to
Alzheimer’s disease. Biol Psychiatry 2008;64:871–879.
23. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity,
diet, and risk of Alzheimer disease. JAMA 2009;302:627–637.
24. Chang-Quan H, Hui W, Chao-Min W, et al. The association of
antihypertensive medication use with risk of cognitive decline
and dementia: a meta-analysis of longitudinal studies. Int J Clin
Pract 2011;65:1295–1305.
25. Martin M, Clare L, Altgassen AM, et al. Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst Rev 2011;(1):CD006220.
26. Petersen RC, Stevens JC, Ganguli M, et al. Practice parameter:
early detection of dementia: mild cognitive impairment (an
evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology
2001;56:1133–1142.
27. Scarmeas N, Stern Y, Mayeux R, et al. Mediterranean diet and
mild cognitive impairment. Arch Neurol 2009;66:216–225.
28. Ooi CP, Loke SC, Yassin Z, et al. Carbohydrates for improving
the cognitive performance of independent-living older adults
with normal cognition or mild cognitive impairment. The Cochrane Database of Syst Rev 2011;13:1-39.
29. Baker LD, Frank LL, Foster-Schubert K, et al. Effects of aerobic
exercise on mild cognitive impairment: a controlled trial. Arch
Neurol 2010;67:71–79.
30. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive
impairment. Cochrane Database Syst Rev 2012;9:Cd009132.
31. Accesed in January 2014: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/
ucm085186.htm
32. Winblad B, Gauthier S, Scinto L, et al. Safety and efficacy of
galantamine in subjects with mild cognitive impairment. Neurology 2008;70:2024–2035.
33. Barnes DE, Yaffe K. Vitamin E and donepezil for the treatment
of mild cognitive impairment. N Engl J Med 2005;353:951-952.
34. Stiles MM, Martin S, Persons RK. Clinical inquiries. Does
treatment with donepezil improve memory for patients with
mild cognitive impairment? J Fam Pract 2006;55:435–436.
35. Newhouse P, Kellar K, Aisen P, et al. Nicotine treatment of mild
cognitive impairment: a 6-month double-blind pilot clinical
trial. Neurology 2012;78:91–101.
36. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev
2007;18:CD003120.
37. Farina N, Isaac M, Clark AR, et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst
Rev 2012;11:CD002854.
38. Smith AD. Homocysteine-lowering by B vitamins slows the rate
of accelerated brain atrophy in mild cognitive impairment: a
randomized controlled trial. PloS one 2010;5:e12244.
39. Ford AH. Vitamins B(12), B(6), and folic acid for cognition in
older men. Neurology 2010;75:1540–1547.
40. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst
Rev 2003;CD004514.
41. Szatmári S, Bereczki D. Procaine treatments for cognition and
dementia. Cochrane Database Syst Rev 2008;CD005993.
42. Flicker L, Grimley Evans G. Piracetam for dementia or cognitive
impairment. Cochrane Database Syst Rev 2011;CD001011.
medicina
universitaria
www.elsevier.com.mx
REVIEW ARTICLE
Trichosporon spp.: an emerging fungal pathogen
A. M. Montoya*, G. M. González
Department of Microbiology, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico
Received: September 2013; Accepted: December 2013
KEYWORDS
Trichosporon; White
piedra;
Onychomycosis;
Trichosporonosis;
Mycoses;
Opportunistic
infection; Mexico.
Abstract Trichosporon spp. has gained importance as the cases of immunosuppressed patients
increase. The genus Trichosporon includes 6 species of clinical relevance that may cause
superficial infections, such as white piedra and onychomycosis, or deep and invasive infections
with high mortality rates. These microorganisms have a broad geographical distribution and
some species are resistant to antifungal drugs in vitro. The present paper is a review on the
virulence factors, associated infections, and in vitro susceptibility of the species with
the highest incidence as pathogenic agents in humans.
Introduction
Trichosporon spp.
Trichosporon spp. was first described by Beigel in 1865
as the agent responsible for a benign hair infection called
white piedra (meaning “stone” in Spanish). Beigel classified the microorganism as algae and placed it in the genus
Pleurococcus. It wasn’t until 1890 when Behrend identified
the microorganism causing white piedra as a fungus which
he called Trichosporon ovoides.1 Although generally associated with this superficial infection, Trichosporon spp. has
gained importance as one of the most opportunistic systemic infections since the first case of invasive trichosporonosis involving the brain, reported in 1970.2
Trichosporon spp. belongs to the phylum Basidiomycota. It
is a yeast-like fungus macroscopically characterized by forming radially symmetrical colonies; these colonies may be
white or yellowish, with a smooth texture, creamy, cerebriform, powdery or moist. Microscopically, Trichosporon
spp. forms hyaline septate hyphae, with abundant arthroconidia and blastoconidia, and in some cases presents appressoria. Regarding physiological tests, they assimilate several
carbohydrates and other carbon sources, yet they do not possess fermentation capabilities. A major characteristic of the
Trichosporon spp. genus is their ability to hydrolize urea.1,3-5
* Corresponding author: Department of Microbiology, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico.
E-mail address: [email protected] (A. M. Montoya).
38
In 1902 Vuillemin grouped the species described for this
genus under the Trichosporon beigelii denomination, a
practice that remained until the late 90’s.5,6 Nevertheless,
posterior classifications at morphological, biochemical, and
molecular levels provided evidence of the existence of more
than one species in the genus.
Approximately 50 species of the genus Trichosporon have
been characterized, 16 of which are associated with diseases in humans. Guého et al. (1994) typified species that had
displayed a major adaptation to the human body: T. asahii,
T. asteroides, T. cutaneum, T. inkin, T. mucoides and T.
ovoides. These 6 species, reclassified from the Trichosporon
beigelii taxon, remain the most relevant clinical species to
date.7
Virulence factors
There is little information regarding virulence factors produced by this microorganism.
Hemolysins, proteases, and lipases allow protein degradation and destabilization of the membranes of the host cell,
increasing fungus pathogenicity. Dağ and Cerikçioğlu analyzed the production of proteases, phospholipases, and esterases of 48 T. asahii clinical isolates, and did not detect
protease nor phospholipase activity in any of the isolates
analyzed; however, all the evaluated strains displayed esterase activity.8 Similarly, Sun et al. evaluated protease, phospholipase, and hemolysine production in 23 T. asahii clinical
isolates, and observed no protease nor phospholipase activity, yet 100% of isolates showed hemolysin activity. This
activity, however, varied for the different T. asahii genotypes identified.9 It is important to underline that there are no
reports about the production of lytic enzymes for Trichosporon non-asahii species.
Phenotypic switching is a fast and reversible change of
colonial morphology and/or microscopic features. These
changes may occur as a response to different environmental
stimuli such as oxidative stress or lack of nutrients, or intrinsic factors such as a mutation in the deoxyribonucleic
acid (DNA) repair systems.10 When phenotypic switching occur in vivo, they involve modifications in the expression of
virulence factors, or alterations in the microorganism-host
cell interactions, thus provoking an increment in the pathogenicity and evasion of the immune response, as observed in
Candida albicans and Cryptococcus neoformans.11-13 Lee et
al., reported phenotypic switching in vitro for the first time
for T. beigelii. The isolated microorganism, recovered from
a patient with a systemic infection, was capable of producing two different morphologies when cultivated at 30°C.
Such morphotypes were accompanied by their respective
structural microscopic changes. Thus, a rough, cerebriform,
moist colony with irregular edges was accompanied microscopically by hyphae while a second powder morphotype,
with a more regular topography and borders, showed microscopically a greater proportion of arthroconidia or blastoconidia. 4 The phenotypic switching was also reported
in vivo by Karashima et al., who performed experiments involving repetitive inoculation of T. asahii in mice. They
observed macro- and microscopic morphological differences
when comparing the fungi before being inoculated and the
same fungi recovered after 3 repetitive passages in 8-week-old
ICR mice. Similar to the results obtained by Lee et al., Karashima observed that the rugged colony was accompanied
microscopically by a greater proportion of hyphae, while a
powdery colony was accompanied by a greater amount of
conidia.14
In the same paper, Karashima et al. reported the production of a cell wall component similar to the glucuronoxylomannan (GXM) of C. neoformans. They observed that a
larger amount of GXM was present in the recovered microorganism after repeated inoculations in mice. GXM has been
proposed to offer C. neoformans protection against phagocytosis by neutrophils and monocytes.14
Another factor providing protection to the fungus is the
formation of biofilms. Some microorganisms have the ability
to produce an extracellular matrix, formed by polysaccharides, proteins, and DNA, which allow conglomeration of cells
and their adherence to both organic and inorganic surfaces.15 Due to the association of invasive infections to the use
of catheters and similar devices, the microorganism’s ability
to adhere itself and form a biofilm could play a very important role in the pathogenesis during trichosporonosis. In
2006, Di Bonaventura et al. assessed the biofilm growth kinetics in vitro for some clinical isolates of T. asahii. They
found that T. asahii cells were capable of quickly adhering
to polystyrene after incubation for 30 minutes, displaying a
low metabolic activity during the first 4 hours. The biofilm’s
complexity increased after 6 to 8 hours of incubation, period during which it was possible to observe a monolayer
formed by filamentous structures. At 72 hours, the cells
showed both yeast-like and filamentous structures embedded in an extracellular matrix, forming a mature biofilm
ranging from 20 to 40 µm in thickness. Biofilm formation
was accompanied by a consequent increase in the resistance to voriconazole (up to 16,000 times more compared to
planktonic cells).16 That same year, Dağ and Cerikçioğlu reported a moderate to weak production of biofilms in 58% of
the clinically isolated T. asahii species that were analyzed.8
Associated infections
Table 1 summarizes the main clinical manifestations and risk
factors in infections caused by Trichosporon spp.
White piedra
White piedra is an infection in which white nodules are formed due to the aggregation of conidia around the hair shaft.
These nodules are soft, whitish, have a defined border, and
measure approximately between 1 and 3 mm of diameter.
White piedra mainly affects capital hair; however, the infection may present itself in the hair of armpits, pubis, and
in a lesser degree moustaches and beards. It is a chronic
and asymptomatic disease. It is a superficial infection in
which fungi remain in contact with the cuticle, without invading neither the hair medulla, scalp, nor skin.3
White piedra is a cosmopolitan and exogenous mycosis occurring more frequently in tropical and temperate climates.
Humidity and poor hygiene are among the risk factors for
the attainment of this pathology. Women and children
are the groups mainly affected by capital white piedra.17,18
Most cases of genital white piedra, second in incidence,
39
Table 1 Infections caused by Trichosporon spp., main clinical manifestations and risk factors.
Principal agents
Transmission
Clinical manifestations
Main risk
factors and
associated
conditions
T. ovoides, T. inkin,
T. cutaneum
Exogenous
White nodules around
parasitized hair
Humidity and
poor hygiene
Shaving the
affected area and
topical imidazoles
T. asahii, T. cutaneum,
T. mucoides, T. inkin
Exogenous
Thickening and discoloration of nails
Humidity and
poor hygiene
Topical imidazoles
Neutropenia and
catheter use
No optimal
treatment exists.
Triazoles have
shown the best
inhibitory effectiveness in vitro
Infection
White piedra
Onychomycosis
Trichosporonosis
T. asahii, T. mucoides,
T. asteroides
Endogenous
Fever, fungemia,
invasion of soft tissues
involve males between 15 and 44 years of age.19,20 T. asahii,
T. inkin, T. cutaneum, T. mucoides, and T. ovoides have all
been associated with white piedra, T. ovoides being the one
with the highest incidence.1,21
Trichosporonosis
When Trichosporon spp. develops as an invasive infection,
the disease is known as trichosporonosis. This infection has
a mortality rate between 50% and 80%,22 and it is the second
or third cause of fungemia in immunocompromised patients
just after Candida spp.23-25 Trichosporonosis is considered an
endogenous disease because the microorganism is commonly found as a part of the flora in the gastrointestinal
tract, lungs, and skin.1,3
These opportunistic systemic infections have gained clinical importance due to their growing prevalence in certain
groups of patients. Neutropenia is the main risk factor. A
relationship between trichosporonosis and having undergone an invasive clinical procedure (e.g., probes and catheters) has been established as well.
Kontoyannis et al. (2004) evaluated risk factors associated
with the infection caused by Trichosporon spp. in 17 cancer
patients. They observed that out of the 10 patients who displayed fungemia, 41% developed trichosporonosis subsequent to the use of catheters. The underlying disease in
most patients was acute leukemia, and in 65% of the cases
neutropenia was observed. Some patients had received chemotherapy (76%) or high doses of corticosteroids (89%)
1 month prior to the trichosporonosis diagnosis.26 Girmenia
et al. (2005) performed a retrospective study including 287
cases of trichosporonosis worldwide. They found that 62.8%
of the patients had suffered from a hematologic disease
previous to the trichosporonosis diagnosis. Acute leukemia
had the highest incidence (68%). Other conditions of risk
associated with the development of trichosporonosis were
solid tumors, transplants, peritoneal dialysis, and human
immunodeficiency virus.27 Ruan et al. (2009), based on a
Treatment
study of 19 cases of invasive trichosporonosis, reported the
use of central catheters as the main risk factor (90%).22 Suzuki et al. (2010) analyzed 33 patients with hematological
diseases; the results were similar to the ones previously reported: acute leukemia (82%) and neutropenia (85%) were
the main risk factors for trichosporonosis. Moreover, it was
observed that most patients were undergoing chemotherapy when diagnosed with this mycosis.28
The main trichosporonosis manifestations are fever and
fungemia. However, tissue invasion may develop. Cases of
inflammation and abscesses in different organs and tissues
(heart, brain, liver, spleen, esophagus, urinary tract, joints,
peritoneum) have been reported. T. asahii, T. asteroides, T.
cutaneum, T. inkin and T. mucoides are the 5 most common
species associated with trichosporonosis cases.9,22,29-32
Tissue invasion and damage
There are reports using murine models for evaluating tissue
damage in invassive infections by Trichosporon spp.. Mice
require cyclophosphamide-induced immunosuppression
prior to high doses of fungi inoculation, which emulates the
neutropenia in patients who develop trichosporonosis.
Studies in animal survival have proven that the establishment of the infection is dose dependent. However, both the
inoculum size causing mortality and time elapsed until tissue invasion is detected vary in different reports. Gokaslan
and Anaissie determined that an inoculum of ≥ 2 x 107 colony
forming units (CFU) causes 100% mortality and invasion of
organs in immunosupressed mice 6 days after infection.34 On
the other hand, Hospenthal et al. reported that an inoculum
of ≥ 7 x 106 CFU caused 100% mortality with tissue invasion 6
hours after infection.35 These models were developed with
infection by T. beigelii, therefore the observed differences in infectivity and progress of the disease could be a result of an induced infection by an unidentified species of the
genus Trichosporon. Yamagata et al. utilized an inoculum of 3 x 106 CFU of T. asahii in a model in which mice were
40
immunosuppressed at week 1, showing a significant difference compared to the animals which were not immunosuppressed or those receiving a second cyclophosphamide dose
at week 3 (20% of mortality). They concluded that the first 3
weeks are critical for the development of systemic trichosporonosis by T. asahii.29
Fungi presence in the affected organs is generalized. Persistence of the microorganism in kidneys of immunosuppressed mice as well as of immunocompetent ones has been
reported. In animal groups where mortality is induced via
inoculation of lethal doses, the initial inoculum has been
recovered as much as 36-fold from brain, heart and kidney.
A resolution of the infection in re-immunosuppressed animals has not been observed. The presence of Trichosporon
spp. has been confirmed by molecular methods, even when
the cell count is under the detection limits.29,34,35
Hyphae and conidia have been observed in different proportions depending on the organ and the stage of infection.
Yeast-like structures are often found in earlier stages, while
hyphae and arthroconidia are present in later stages of the
infection. Predominance of yeast-like structures in the lungs
of the infected animals has been reported.35
One of the most prevalent signs of invasive trichosporonosis is the granulomatous inflammation reported in lungs, liver, lymph nodes, and spleen in immunosuppressed and
immunecompetent mice, as well as a fungal invasion of the
blood vessels’ lumen or periphery.34-36
Other findings include kidney, spleen, lung, and heart hyperemia. Tubular edema, focal parenchymal destruction,
cortical tubular necrosis, and chronic inflammation with fibrosis have been observed in the kidneys of mice surviving
infection. In the liver, hepatic sinus dilation and congestion
have been reported, as well as degeneration and necrosis of
some hepatocytes and proliferation of Kupffer cells. Splenic
sinuses dilation and splenomegaly have also been observed.
In lungs, edema, hemorrhage, and alveolar ectasia have
been described. In the heart, evidence of hemorrhage and
cardiomyocytes necrosis have been reported. 34-37
Onychomycosis
In the last few years, cases of onychomycosis associated
with infections caused by Trichosporon spp. have increased.
Around the world, this genus is the agent responsible for
1.3% to 10% of onychomycosis cases, being T. asahii, T. mucoides, and T. inkin the most frequently involved microorganisms.38-40 There have been discrepancies between cases
reported in Mexico and other countries. In a study performed in pediatric patients from a rural area, Archer-Dubon
et al. isolated T. cutaneum in 42% of the patients with
onychomycosis and athlete’s foot, a percentage higher than
the estimated for infections by dermatophytes and Candida
spp., microorganisms typically responsible for foot infections.41
Laboratory diagnosis
Clinical laboratory diagnosis varies in cases of superficial
and systemic infections. In the case of white piedra, the
hair sample is submerged in a potassium hydroxide solution
for observation under the microscope of the nodules formed
by the aggregated spores around the hair shaft, which
allows differential diagnosis of other parasitizations such as
pediculosis or trichomycosis. Similarly, onychomycosis diagnosis requires the nail scrape to be submerged in potassium hydroxide for microscopic observation of conidia and
hyphae. In both cases, precise etiologic diagnosis requires a
culture. Trichosporonosis diagnosis is made routinely by the
recovery of fungi from blood and/or biopsies.3
Cultures obtained from diverse clinical samples are used
for identifying the etiologic agent through its microscopic
morphology by confirming the presence of the 3 characteristic structures of the genus Trichosporon: hyphae, arthrocondia, and blastocondia. The biochemical profile may be
obtained by auxanography, which evaluates the ability to
assimilate different sources of carbon. However, the complete biochemical characterization of species of the genus
Trichosporon is based on the assimilation of approximately
50 carbon compounds and requires anywhere between 5 and
15 days for the readings; consequently, it is not practical to
carry out this battery of tests for the precise identification
of pathogenic species. There are commercial methods
which systematize the application of assimilation tests and
reduce the required identification time. The API 20C AUX
system by bioMérieux is a commercial micromethod, which
has turned into the most used in clinical laboratories. This
system evaluates the assimilation ability of 19 carbohydrates and allows identification within a timeframe of 24 to 72
hours of incubation. However, a limitation of this test is that
it only allows the identification of 3 species of the genus: T.
asahii, T. inkin, and T. mucoides. This last characteristic
prevents its generalized use.
Different molecular methods have been developed as fast
and effective alternatives for the precise identification of
many pathogens at the species level. Ribosomal DNA is widely used in the systematic identification of microorganisms. Molecular identification of fungi is typically performed by sequencing of the internal transcribed spacer (ITS)
region. One of the inconveniences of this region is the fact
that it is highly homologous between the different species
in the genus Trichosporon; therefore, the analysis of other
genes or regions with higher heterology is needed in order to obtain a more accurate identification. Sugita et al.
analyzed 84 strains corresponding to 25 species of the genus
Trichosporon to evaluate the efficacy of sequencing the ITS
region and the intergenic spacer 1 (IGS1) region for the precise identification at a species level. They found a higher
heterology between IGS1 regions in comparison to ITS. This
makes the IGS1 sequencing analysis superior compared to
ITS for the differentiation between species of the genus. In
addition, this method allows genotypification.42
A growing number of reports reveal the effectiveness of
molecular methods in the identification of this microorganism. These publications show the lack of specificity of the
conventional identification methods based in morphologic
and biochemical criteria.43-46
Treatment
Superficial infections caused by Trichosporon spp. may be
treated with galenic solutions such as 1% mercuric chloride, 1% iodine solution, and 30% salicylic acid. They may be
41
treated with topical antifungals, mainly imidazoles like econazole, isoconazole, miconazole, and ketoconazole. In patients with white piedra, the trimming or shaving of
parasitized hairs or affected areas prior to topical treatment
is recommended.1,3,17
Management of deep infections has been a bigger challenge. Trichosporon spp. has displayed variable resistance to
the most common antifungal treatments; consequently, there is no optimal treatment for trichosporonosis cases.
5-Flucytosine (5-FC) is an inhibitor of the synthesis of nucleic acids; it interacts with the fungal RNA disrupting the
synthesis of proteins. 5-FC has shown poor antifungal activity against the most clinically relevant species, with MICs ≥ 2
µg/ml and reaching concentrations of up to 128 µg/ml for T.
mucoides.9,22,44,49
Caspofungin (CAS) is an echinocandin that inhibits the
synthesis of the fungal cell wall. CAS MICs are high for T.
asahii (≥ 4 µg/ml) and T. asteroides (16 µg/ml).49,50
In vitro susceptibility
Immunotherapy
Trichosporon spp. was first reported as an amphotericin Bresistant pathogen by Walsh et al. in 1990, after evaluating
2 T. beigelii isolates obtained from patients with systemic
infections.47 Since its taxonomic revision, several studies
have assessed the efficacy of different antifungals against
the species of the genus, mainly T. asahii.
It is important to mention that to this day there is not an
established method to determine in vitro susceptibility of
species belonging to the genus Trichosporon. The most widely
used protocol is an adaptation of the method used for Candida spp. and C. neoformans described in documents M27 and
M44 of the Clinical and Laboratory Standards Institute.
One of the most evaluated antifungals has been amphotericin B (AMB). This is a polyenic derivate that destabilizes
the fungal cytoplasmic membrane; it is the treatment of
choice for systemic infections. The resistance of Trichosporon spp. to AMB has been reported. T. asahii consistently
exhibits a MIC of ≥ 2 µg/mL (Minimal Inhibitory Concentration, which prevents visible growth of 90% of isolates).22,44,48,49 There are similar MICs for other clinical isolates
including T. asteroides, T. cutaneum, and T. ovoides.22 Rodríguez-Tudela et al. (2005), contrary to the previous study,
reported low MICs for T. cutaneum (0.25-0.5 µg/ml) and T.
ovoides (0.37 µg/ml). T. mucoides showed great variability
regarding susceptibility to AMB, with MICs ranging between
0.015 and 16.0 µg/ml.44 T. inkin is the species which has
displayed greater in vitro susceptibility to the inhibitory activity of AMB, with MICs from 0.14 to 1.0 µg/ml.44,48
Triazolic compounds are inhibitors of the ergosterol
synthesis, the main component of the fungal cytoplasmic
membrane. In addition, they interact with enzymes at a mitochondrial level causing the accumulation of free radicals
inside the cell and provoking the inhibition of fungal growth.
Triazolics include fluconazole (FLC), voriconazole (VRC),
itraconazole (ITR), and posaconazole (POS). These agents
have displayed better in vitro activity against Trichosporon
spp., with relatively low MICs for T. asahii (FLC 1.27 to ≤
10.3 µg/ml, ITR ≤ 1.4 µg/ml, POS 0.25 µg/ml), T. asteroides
(FLC 0.8 µg/ml, ITR 0.06 µg/ml), T. inkin (FLC ≤ 4 µg/ml,
ITR ≤ 1 µg/ml), T. cutaneum (FLC ≤ 32 µg/ml, ITR ≤ 1 µg/
ml), and T. ovoides (FLC 1.74 µg/ml, ITR 0.1 µg/ml).22,44,48,49
Voriconazole is particularly effective for fungal inhibition in
vitro, with MICs of ≤ 0.28 µg/ml for the 6 more frequently
isolated Trichosporon species causing human pathology.44,49
Terbinafine (TER) is a synthetic antifungal derived from
allylamines that inhibits ergosterol synthesis. TER requires
high concentrations in order to inhibit T. asahii (12.6 µg/
ml), as opposed to the inhibition of T. cutaneum o T. inkin (1
µg/ml).48
Since neutropenia is the main condition associated with the
development of trichosporonosis, the use of cytokines has
been considered for the treatment of these infections.
Some of the factors used are the granulocytes colony stimulating factors (G-CSF), which increase polymorphonuclear
cell count, and the granulocytes-macrophages colony stimulating factors (GM-CSF), which activate monocytes and macrophages functions. Muranka et al. (1997) used a murine
model with disseminated T. asahii trichosporonosis for the
evaluation of G-CSF and GM-CSF as therapy against systemic
infection. They observed that the use of G-CSF prior to
fungal infection increased the survival in mice from 25%
to 100%, decreasing the fungal load and tissue damage in
affected organs, with the most notable improvement in the
lungs. The increase in neutrophils by GM-CSF was lower than
the one caused by G-CSF, so the use of GM-CSF therapy did
not generate any major improvements in animals. In the
same study, they observed an increase of tumor necrosis
factor alpha (TNF-α) in bronchoalveolar lavage fluid in mice
infected with lethal doses of T. asahii and treated with GMCSF compared to non-immunosuppressed animals or animals
treated with G-CSF. In addition, a negative correlation between TNF-α production and the presence of leukocytes in
peripheral blood was observed, decreasing as mice recuperated from the neutropenia. Anti-TNF-α therapy did not favor infection resolution. The investigators concluded that
neutrophil count was the most critical factor in the development of trichosporonosis; however, other factors, such as
TNF-α in lung, played an important role in the resolution of
the infection.51
Similarly, the use of macrophages colony stimulating factor
(M-CSF) has been evaluated as an activator of phagocytosis in
a trichosporonosis murine model with T. asahii. M-CSF increased fungicidal activity in mononuclear cells, with a notable
increase in survival and a decrease in fungal load. In addition,
an increase in TNF-α in lungs and plasma in animals treated
with M-CSF was noticeable. Different from the results reported by Muranaka et al., anti-TNF-α treatment did increase
survival in mice. Results showed how M-CSF exponentially increased fungal activity by mononuclear phagocytes, helped
partly by the production of TNF-α.52
Similar results regarding the effect of G-CSF, GM-CSG, and
M-CSF on leukocytes and their role in trichosporonosis resolution were reported by Roilides et al. (2002).53
Conclusion
Vast distribution, antifungal resistance, and an increase in
the number of patients presenting risk factors have made
42
relevant the study of species belonging to the genus Trichosporon as opportunistic fungal agents relevant. High mortality rates in patients with systemic infections as well as a lack
of an optimal treatment generate the need to increase the
knowledge of this particular pathogen, in a way that allows
us to understand its virulence mechanisms, and consequently, to obtain the necessary tools for the development
of effective therapies against these microorganisms.
Funding
References
1. Colombo AL, Padovan ACB, Chaves GM. Current knowledge of
Trichosporon spp. and trichosporonosis. Clin Microbiol Rev
2011;24:682–700.
2. Watson KC, Kallichurum S. Brain abscess due to Trichosporon
cutaneum. J Med Microbiol 1970;3:191–193.
3. Bonifaz A. Micología médica básica. México: McGraw Hill/Interamericana; 2012. p. 161-168.
4. Lee JW, Melcher GA, Rinaldi MG, et al. Patterns of morphologic
variation among isolates of Trichosporon beigelii. J Clin Microbiol 1990;28:2823–2827.
5. Guého E, de Hoog GS, Smith MT. Neotypification of the genus
Trichosporon. Antonie van Leeuwenhoek 1992;61:285–288.
6. Guého E, Smith MT, de Hoog GS, et al. Contributions to a revision of the genus Trichosporon. Antonie van Leeuwenhoek
1992;61:289–316.
7. Guého E, Improvisi L, de Hoog GS, et al. Trichosporon on humans: a practical account. Mycoses 1994;37:3–10.
8. Dağ A, Cerikçioğlu N. Investigation of some virulence factors of
Trichosporon asahii strains isolates from the clinical samples of
hospitalized patients. Mikrobiyoloji Bülteni 2006;40:225–235.
9. Sun W, Su J, Xu S, et al. Trichosporon asahii causing nosocomial
urinary tract infections in intensive care unit patients: genotypes, virulence factors and antifungal susceptibility testing. J
Med Microbiol 2012;61:1750–1757.
10. Alby K, Bennett RJ. Stress-induced phenotypic switching in
Candida albicans. Mol Biol Cell 2009;20:3178–3191.
11. D’Souza CA, Heitman J. It infects me, it infects me not: phenotypic switching in the fungal pathogen Cryptococcus neoformans. J Clin Invest 2001;108:1577–1578.
12. Geiger J, Wessels D, Lockhart SR, et al. Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by
white-opaque switching in Candida albicans. Infect Immun
2004;72:667–677.
13. Kumamoto CA, Vinces MD. Contributions of hyphae and hyphaco-regulated genes to Candida albicans virulence. Cell Microbiol 2005;7:1546–1554.
14. Karashima R, Yamakami Y, Yamagata E, et al. Increased release
of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice. J Med
Microbiol 2002;51:423–432.
15. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms:
from the natural environment to infectious diseases. Nat Rev
Microbiol 2004;2:95–108.
16. Di Bonaventura G, Pompilio A, Picciani C, et al. Biofilm formation by the emerging fungal pathogen Trichosporon asahii:
development, architecture, and antifungal resistance. Antimicrob Agents Chemother 2006;50:3269–3276.
17. Kiken DA, Sekaran A, Antaya RJ, et al. White piedra in children.
J Am Acad Dermatol 2006;55:956–961.
18. Vieira da Silva Pontes ZB, Lira Ramos A, de Oliveira Lima E, et al.
Clinical and mycological study of scalp white piedra in the state
of Paraíba, Brazil. Mem Inst Oswaldo Cruz 2002;97:747–750.
19. Kalter DC, Tschen JA, Cernoch PL, et al. Genital white piedra:
Epidemiology, microbiology, and therapy. J Am Acad Dermatol
1986;14:982–993.
20. Schwinn A, Ebert J, Hamm H, Bröcker EB. Genitale weisse Piedra. Der Hautarzt 1996;47:638–641.
21. Shivaprakash MR, Singh G, Gupta P, et al. Extensive white piedra of the scalp caused by Trichosporon inkin: A case report and
review of literature. Mycopathologia 2011;172:481–486.
22. Ruan SY, Chien JY, Hsueh PR. Invasive trichosporonosis caused
by Trichosporon asahii and other unusual Trichosporon species
at a medical center in Taiwan. Clin Infect Dis 2009;49:e11–e17.
23. Córdoba S, Vivot W, Bosco-Borgeat ME, et al. Species distribution and susceptibility profile of yeasts isolated from blood cultures: results of a multicenter active laboratory-based surveillance study in Argentina. Rev Argent Microbiol 2011;43:176–
185.
24. Dotis J, Pana ZD, Roilides E. Non-aspergillus fungal infections in
chronic granulomatous disease. Mycoses 2013;56:449-462.
25. Oberoi JK, Wattal C, Goel N, et al. Non-albicans Candida species in blood stream infections in a tertiary care hospital at
New Delhi, India. Indian J Med Res 2012;136:997–1003.
26. Kontoyiannis DP, Torres HA, Chagua M, et al. Trichosporonosis in
a tertiary care cancer center: risk factors, changing spectrum
and determinants of outcome. Scand J Infect Dis 2004;36:564–
569.
27. Girmenia C, Pagano L, Martino B, et al. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin
Microbiol 2005;43:1818–1828.
28. Suzuki K, Nakase K, Kyo T, et al. Fatal Trichosporon fungemia in
patients with hematologic malignancies. Eur J Haematol
2010;84:441–447.
29. Yamagata E, Kamberi P, Yamakami Y, et al. Experimental model
of progressive disseminated trichosporonosis in mice with latent trichosporonemia. J Clin Microbiol 2000;38:3260–3266.
30. Heslop OD, Nyi Nyi MP, Abbott SP, et al. Disseminated trichosporonosis in a burn patient: meningitis and cerebral abscess due
to Trichosporon asahii. J Clin Microbiol 2011;49:4405–4408.
31. Matsue K, Uryu H, Koseki M, et al. Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. Clin Infect Dis 2006;42:753–757.
32. Rastogi VL, Nirwan PS. Invasive trichosporonosis due to Trichosporon asahii in a non-immunocompromised host: a rare case
report. Indian J Med Microbiol 2007;25:59–61.
33. Kalawat U, Sharma KK. Trichosporon peritonitis following duodenal perforation. Saudi J Gastroenterol 2010;16:43–45.
34. Gokaslan A, Anaissie E. A novel murine model of disseminated
trichosporonosis. Infect Immun 1992;60:3339–44.
35. Hospenthal D, Belay T, Lappin P, et al. Disseminated trichosporonosis in a neutropenic murine model. Mycopathologia
1993;122:115–122.
36. Lacy SH, Gardner DJ, Olson LC, et al. Disseminated trichosporonosis in a murine model of chronic granulomatous disease.
Comp Med 2003;53:303–308.
37. Lin YP, Yang YP, Huang WM, et al. Experimental pathogenicity of
a clinical isolate of Trichosporon dermatis in a murine model.
Mycopathologia 2011;172:381–387.
38. Dhib I, Fathallah A, Yaacoub A, et al. Clinical and mycological
features of onychomycosis in central Tunisia: a 22 years retrospective study (1986-2007). Mycoses 2012;56:273–280.
39. Pontes ZB, Lima Ede O, Oliveira NM, et al. Onychomycosis in
João Pessoa City, Brazil. Rev Argent Microbiol 2002;34:95–99.
40. Kim ES, Kim DH, Chang SE, et al. Trichosporon species in
onychomycosis and tinea pedis. Korean J Dermatol
2003;41:702–707.
41. Archer-Dubon C, Orozco-Topete R, Leyva-Santiago J, et al. Superficial mycotic infections of the foot in a native pediatric population: a pathogenic role for Trichosporon cutaneum? Pediatr
Dermatol 2003;20:299–302.
42. Sugita T, Nakajima M, Ikeda R, et al. Sequence analysis of the
ribosomal DNA intergenic spacer 1 regions of Trichosporon species. J Clin Microbiol 2002;40:1826–1830.
43. Middelhoven WJ, Scorzetti G, Fell JW. Systematics of the anamorphic basidiomycetous yeast genus Trichosporon Behrend
with the description of five novel species: Trichosporon vadense, T. smithiae, T. dehoogii, T. scarabaeorum and T. gamsii. Int
J Syst Evol Microbiol 2004;54:975–986.
44. Rodriguez-Tudela JL, Diaz-Guerra TM, Mellado E, et al. Susceptibility patterns and molecular identification of Trichosporon
species. Antimicrob Agents Chemother 2005;49:4026–4034.
45. Ahmad S, Al-Mahmeed M, Khan ZU. Characterization of Trichosporon species isolated from clinical specimens in Kuwait. J Med
Microbiol 2005;54:639–646.
46. Taj-Aldeen SJ, Al-Ansari N, El Shafei S, et al. Molecular identification and susceptibility of Trichosporon species isolated from
clinical specimens in Qatar: isolation of Trichosporon dohaense
Taj-Aldeen, Meis & Boekhout sp. nov. J Clin Microbiol
2009;47:1791–1799.
43
47. Walsh TJ, Melcher GP, Rinaldi MG, et al. Trichosporon beigelii,
an emerging pathogen resistant to amphotericin B. J Clin Microbiol 1990;28:1616–1622.
48. Li HM, Du HT, Liu W, et al. Microbiological characteristics of
medically important Trichosporon species. Mycopathologia
2005;160:217–225.
49. Chagas-Neto TC, Chaves GM, Melo ASA, Colombo AL. Bloodstream infections due to Trichosporon spp.: species distribution,
Trichosporon asahii genotypes determined on the basis of ribosomal DNA Intergenic Spacer 1 Sequencing, and antifungal susceptibility testing. J Clin Microbiol 2009;47:1074–1081.
50. Guo LN, Xiao M, Kong F, et al. Three-locus identification, genotyping, and antifungal susceptibilities of medically important
Trichosporon species from China. J Clin Microbiol 2011;49:3805–
3811.
51. Muranaka H, Suga M, Nakagawa K, et al. Effects of granulocyte
and granulocyte-macrophage colony-stimulating factors in a
neutropenic murine model of trichosporonosis. Infect Immun
1997;65:3422–3429.
52. Sasaki E, Tashiro T, Kuroki M, et al. Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii. Clin Exp Immunol 2000;119:293–298.
53. Roilides E, Gil Lamaignere C, Farmaki E. Cytokines in immunodeficient patients with invasive fungal infections: an emerging
therapy. Int Journal Infect Dis 2002;6:154–163.
medicina
universitaria
www.elsevier.com.mx
Standards for authors
Manuscripts should be written in line with the recommendations of the International Committee of Medical Magazines
Publishers (N Engl J Med 1997;336:309-15) and articles should adhere to the following rules:
1. The text should be delivered in printed letter size
sheets (21 × 27 cm [8.5 × 11 inches]). Use “Times New
Roman” type (title in 14 points size, and text in 12
points size), and use double spacing. Printed sheets
must be accompanied by a CD (Compact Disc) with
the corresponding text captured, and having a label
indicating the following: the title of the article, main
author’s name, and computer program used (including
the number version). Example: Estrogen in menopause. Guillermo Martinez. Word (6.0). The articles
should be preferably in English, nevertheless, Spanish
written papers will be accepted, but the author must
accept the translation that the Editorial Board determines.
2. Text sections should be sequenced as follows: Title
page, Summary (in Spanish), Abstract (in English),
Introduction, Materials and methods, Results, Discussion, References, Tables, Illustrations feet.
3. Original articles should be no longer than 30 pages.
Presentations of clinical cases should be written in 16
or less pages. Review articles won’t be longer than 30
pages. Finally, the maximal length of the letters to
the Editor will be 30 pages.
4. Front page should include full title of the work (in
no more than 85 characters), author(s)’ names and
their professional credits (including work function
in services or departments and institution[s] where
they work), and mail address of the main author. If
authors serve in various services in the same institution, institution’s name is to be written once below
the authors list, with superscript numbers for identification.
5. For identification purposes,write mais author�s name
and surname in the left side of the heading of every
page, and progressive page number in the right extreme of the heading.
6. All artwork (one color or full color) must be presented in printed slides sharp and well-definded. On the
slide frame, write by hand the keywords for the article identification, illustration number, main author�s
surname and an arrow signaling the top of the figure. When using illustrations previously published, you
must add the written consent from the copyright holder. Insted of slides, you may deliver printed copies in
high definition.
7. Images, drawings and other graphic material must be
professionally drawn or elaborated through a computer program in TIFF (300 dpi) format, and attach
at the end of the corresponding file in the CD, labeling
them and specifying the computer program used.
8. Tables shall be numbered in Arabic characters. Each
one must hold a brief, self-documenting title, as well
as information of the place and year of the study, when
applicable; at the foot of this title, notes should be
included to explain uncommon abbreviations. Don’t
use horizontal nor vertical lines inside the tables. All
tables must be quoted in the body text. The maximal
acceptable quantity of tables equals the number of
the double-spaced pages divided by two, minus one,
excluding front page and references or bibliography.
Example: 10 pages text = 4 graphs or tables (as a whole); 16 pages text = 7 graphs or tables. Don’t deliver
photos of tables.
9. Kinds of articles: this magazine publishes: original
articles on clinical or laboratory research, editorials,
biotechnology, review articles, scientific letters. The
Editor accepts items written in English or Spanish.
10.Summary (in Spanish). The second page should include a summary in no more than 250 words. This summary must be structured as follows: objective, material and methods, results and conclusions. Summary
should present clearly the purposes, basic procedures,
methodology, main findings (speciic data and its statistical significances), as well as the most important conclusions. 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
of the summary.
12.Body text. Experimental or observational items must
include introduction, materials and methods, results
and discussion. Other kinds of articles, as cases reports,
1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados.
Standards for authors
review articles and editorials, will include introduction, development and conclusions.
13.Introduction. This is a brief presentation of the purpose of the article. It contains an outline of the rationale
used for the study or observation. Mention strictly relevant references, without a comprehensive review of
the topic. Do not include here data or conclusions
of the work you are presenting.
14.Material and methods. Make a clear description of the
method for selecting subjects to be observed or their
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
allow other researchers to replicate the results. Explain briefly methods already published, but not well
known yet. Describe new or substantially modified
methods, indicating the rationale for using them, and
evaluate their limitations. Identify exactly all drugs
and chemicals by generic names, dose and routes of
administration. Include the ethical aspects of your
study (protocol approved by ethics or research commissions or committees, informed consent). Describe
the statistical management of data and indicate the
statistical package you used.
15.Results. Present them in a logical sequence. Don’t
repeat data included in the tables or figures; only
highlight or summariza important observation.
16.Discussion. Compare the results of your study with
others already published, expressing consistencies
and differences among trials. Emphasize new and
important aspects in your research. Don’t repeat detailed data or other information already presented in
previous sections. Explain the meaning of the results
and their limitations, including implications for future
research. Set the link between the conclusions and
the goals of the study, and do not make general statements or conclusions without a foundation. Set for
new hypothesis when there is a justification to do so.
17.References. Number references consecutively, following the order in which they appear in the article
(identify quotations in the text through superscript
numbers; don’t use parentheses). In texts followed
by a punctuation mark (period, comma, colon, semicolon), the quotation numbers will be written after
the punctuation mark. For references to the name
of the magazine, use abbreviations listed in the Index
Medicus, on the January issue published each year.
Don’t use the term “personal communication”. On he
contrary, the expression “in press” is allowed when it
refers to a text already accepted by some magazine.
When information comes from a text sent to a magazine, but not accepted yet, it should be quoted as “unpublished observations”. All authors of quoted articles
shall be mentioned if they are six or less; however, if
the item was written by seven or more authors, relate
only the first three, followed by the words et al. If the
referred article was published in a supplement, add
the text Suppl X between the volume number and the
first page.
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
follows:
21.Hernández RF. Manual de anatomía. 2ª Edición. México: Méndez Cervantes; 1991: 120-9.
22.References to one chapter of a book should include:
chapter authors’ name, article name, country of the
publishing company, publishing company, year of publication, and relevant pages.
23.Copyright transmission. Every article must have attached a letter signed by all authors, containing the following text: “I/we s transfer all commercial rights to
the University Medicine Magazine, that becomes the
owner of all materials submitted to them for publication”. This transference will be effective only for
works published by the magazine. Material published
in the Magazine can’t be reproduced without permission.
24.The University Medicine Magazine has the right to
make changes or amendments to the manuscript,
for the sake of a better understanding of the article,
without changing the contents of the item.
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/

"dr. josé eleuterio gonzález" university hospital univers

Transcription

Similar documents

Escola Secundária José Gomes Ferreira

What is race discrimination? - ACT Human Rights Commission

information exchange policy vocabulary (iepv)

2016 Post Show Report

dr. blum invitation

Washington Attorneys Assisting Community Organizations (WAACO)

dementia - Frye Art Museum

Historical AIB Certificates

Presentation