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BOLETIN
Médico Científico de la Asociación Médica de Puerto Rico
Año 2013 - Volumen 105 - Número 3
Contenido
Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus
No. ISSN-0004-4849. Registrado en Latindex -Sistema Regional de Información en Línea para
Revistas Científicas de América Latina, el Caribe, España y Portugal
Mensaje del Presidente
5
Coaliciones en favor de los pacientes
Natalio Izquierdo Encarnación, MD
Original Article/Artículos Originales
9
Breast Asymmetry Pattern In Women With
Idiopathic Scoliosis
Norma I. Cruz MD, Leo Korchin DDS
Case Reports / Reporte de Casos
43
Exacerbation Of Mood Symptoms Associated To Primary And Secondary Carnitine
Deficiency: A Case Report
45
Rectovestibular Fistula With Normal Anus: A
Treatment Alternative
Javier Santos-Cubiña MD, Alexis Torres- Rodríguez MD,
Pedro A. Castaing-Cespier MD, Nuria Sabaté MD, Ana Torres-Martín MD, Simón Carlo MD
Anwar Abdul-Hadi MD, Humberto Lugo-Vicente MD
13
Pregnancy Outcomes And Sucessful Rate Of
Nifedipine Therapeutic Protocol Implementation
In A Hospital Of San Juan
50
An Unexpected Side-Effect Of A Commonly Used Drug
17
Magnesium: The Forgotten Electrolyte
Menstrual Psychosis: Presenting Symptom Of
Bipolar Disorder Not Otherwise Specified In A
13-Years-Old Hispanic Female
21
Comparison Of The Appropriate Use Of
Antibiotics Based On Clinical Guidelines
Between Physicians In-Training Versus
Practicing Physicians
53
25
Pregnancy And Neonatal Outcomes Of Women
Receiving Compounded 17-@ Hydroxyprogresterone At San Juan City Hospital
29
36
Leonardo N. Catalano MD, Michelle Villar Díaz MD, Miguel Vázquez Guzmán MD, Ivette Negrón MS, Edgardo Rivera Rosa MD
Wilma González BS, Pablo I. Altieri MD, Silo Alvarado MSII, Héctor
L. Branchs MD, Nelson Escobales PhD, María Crespo PhD, William Borges MD
Francisco Fernández González MD, Javieth Detrés MD, Pedro
Torrellas MD, Carmen R. Ballester MD
Olga M. Pereira MD, Soan G. Cruz Ortiz MD, Amaury Llorens MD,
Edgardo Rivera Rosa MD
Profile Of Patients Admitted With Infected Skin
Ulcers At Bella Vista Hospital Mayaguez
Brandie Austidillo MD, Miguel Cruz MD, Luis del Prado MD,
Renato Domenack MD, Eva Nasi MD, Sergio Sede MD,
R. Iván iriarte MD
Inicios De Validación De La Escala Para Medir
Calidad De Vida En Pacientes Con Cancer
Janelly Muriel Sanoguet MS, José Rodríguez Gómez MD
ILUSTRACION DE PORTADA
Jorge Acevedo Canabal
Patients
Ilustración digital de cubierta realizada por Juan Laborde-Crocela y diseño gráfico de Alberto Ignacio González en la Oficina
de Informática de la AMPR. Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto Rico
E-mail:[email protected]
Francisco Fernández González MD, Samayra Miranda MD,
Mónica Santiago Casiano MD, José Nieves MD, Edgardo Adorno MD, Ricardo Fernández González MD
Javier Santos-Cubiña MD, Pedro A. Castaing-Lespier MD,
Nuria Sabaté MD, Ana Torres- Martín MD, Virgen M. QuiñonesFernandini MD
Review Article/Artículo de Reseña
56
Ethnicity And Genetics Are More Important Than Diabetes Mellitus And
Hypertension In Producing Cardiovascular Events In Patients With The Metabolic Syndrome: Emphasis In The Puerto Rico
Population
64
Pulmonary Lymphagioleyomyomatosis:
Literature Update 70
Variaciones Anatómicas De La Arteria Carotida Interna: Implicaciones Para El Terapista
Endovascular Neurológico
Pablo I. Altieri MD, José M. Marcial MD, Héctor Banchs MD,
Nelson Escobales PhD, María Crespo PhD
Samuel Valentín-Mendoza MD, José Nieves Nieves MD,
Rosángela Fernández-Medero MD, Ricardo Fernández-Gonzáles MD, José Adorno Fontánez MD, Edgardo Adorno Fontánez MD
Marco Zenteno, Angel Lee, Luis Rafael Moscote-Salazar
OFICINAS ADMINISTRATIVAS
SUBSCRIPCIONES Y ANUNCIOS
Asociación Médica de Puerto Rico
PO Box 9387 • SANTURCE, Puerto Rico 00908-9387
Tel 787-721-6969 • Fax: 787- 724-5208
Email: [email protected]
ANUNCIOS EN BOLETIN, WEBSITE
y NEWSLETTER
Tel.: (787) 721-6939
Web Site: www.asocmedpr.org
4
Asociación Médica de Puerto Rico
JUNTA DE DIRECTORES
Dr. Natalio Izquierdo Encarnación
Dra. Wanda G. Vélez Andújar
Dr. Raúl G. Castellanos Bran
Dr. Pedro J. Zayas Santos
Dra. Ilsa Figueroa Dra. Hilda Ocasio Maldonado
Dr. Raúl A. Yordán Rivera
Dr. Jaime M. Díaz Hernández
Dr. Arturo Arché Matta
Dr. Juan Rodríguez Del Valle
Dr. Gonzalo González Liboy
Dr. Rolance G. Chavier Roper
Dr. Ricardo Marrero Santiago
Dr. Rafael Fernández Feliberti
Dra. Mildred R. Arché
Dr. Salvador Torrós Romeu
Dra. Daisy Quirós
Presidente
Pres. Electo
Presidente Saliente
Tesorero
Secretaria
Vicepresidenta AMPR
Vicepresidente AMPR
Vicepresidente AMPR
Pres. Cámara Delegados
Vicepres. Cámara Delegados
Delegado AMA
Delegado AMA
Delegado Alt. AMA
Delegado Alterno AMA
Pres. Distrito Central
Pres. Distrito Este
Pres. Distrito Sur
JUNTA DE EDITORES
Objetivos
Humberto Lugo Vicente, MD, Presidente
Luis Izquierdo Mora, MD
Melvin Bonilla Félix, MD
Carlos González Oppenheimer, MD
Eduardo Santiago Delpin, MD
Francisco Joglar Pesquera, MD
Yocasta Brugal, MD
Juan Aranda Ramírez, MD
Francisco J. Muñiz Vázquez, MD
Walter Frontera, MD
Mario. R. García Palmieri, MD
Natalio Izquierdo Encarnación, MD
José Ginel Rodríguez, MD
La Asociación Médica de Puerto Rico es fundada
en el año de 1902, cuando por aquel entonces, el
insigne doctor Manuel Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad
y así fomentar el contínuo progreso de la ciencia y
el arte de la medicina y el mejoramiento de la salud
del pueblo de Puerto Rico. Tras vencer incontables
dificultades e inconvenientes naturales de la época,
se celebró la asamblea constituyente el día 21 de
septiembre de 1902, en el salón de sesiones de la
Cámara de Delegados en la ciudad de San Juan.
Reserva de derechos
El “Boletín” se distribuye a los médicos y estudiantes de medicina de Puerto Rico y se publica en versión digital en
www.asocmedpr.org.
Todo anuncio que se publique en el Boletín de la Asociación Médica de Puerto Rico deberá cumplir con las normas
establecidas por la Asociación Médica de Puerto Rico y la Asociación Médica Americana.
La Asociación Médica de Puerto Rico no se hace responsable por los productos o servicios anunciados.
La publicación de los mismos no necesariamente implica el endoso de la Asociación Médica de Puerto Rico.
Todo anuncio para ser publicado debe reunir las normas establecidas por la publicación. Todo material debe entregarse listo para la imprenta y con sesenta días de anterioridad a su publicación.
La AMPR no se hará responsable por material y/o artículos que no cumplan con estos requisitos.
Todo artículo recibido y/o publicado está sujeto a las normas y reglamentos de la Asociación Médica de Puerto Rico.
Ningún artículo que haya sido previamente publicado será aceptado para esta publicación. La Asociación Médica de
Puerto Rico no se hace responsable por las opiniones expresadas o puntos de vista vertidos por los autores, a menos
que esta opinión esté claramente expresada y/o definida den tro del contexto del artículo.
Todos los derechos reservados. El Boletín está totalmente protegido por la ley de derechos del autor y ninguna persona o entidad puede reproducir total o parcialmente el material que aparezca publicado sin el permiso escrito de los
autores.
Mensaje del
Presidente
5
Natalio Izquierdo
Encarnación, MD
Infraestructura Sanitaria y la
Salud
Me preocupa la salud de este pueblo y particularmente en este momento la calidad de las
aguas.
Durante el mes de julio de este año, vimos en
los rotativos del país alarmantes noticias sobre
la calidad de las aguas. La Junta de Calidad
Ambiental reportó que los ríos de la Isla estaban contaminados por la presencia de metales
y coliformes. La realidad está clara. Los cuerpos de agua de nuestro país, que los taínos
llamaban Isla de los Ríos, están enfermos. Ya
en el 2010, cerca del 60% de los ríos y quebradas de Puerto Rico, no están en cumplimiento
con la Junta de Calidad Ambiental.
Días más tarde, el mismo periódico del País,
reportó la contaminación de las playas de la
Isla, secundario a las lluvias. Estas publicaciones me preocupan porque se ven en todas
partes del mundo. Dicho artículo mencionaba
19 balnearios contaminados. Esto afecta el
turismo de la Isla. Es cierto, la Junta de Calidad Ambiental ha reportado que el 36% de
las Aguas costeras, no cumplen con los estándares de EPA y de la Junta.
Se sabe que en Puerto Rico, hay comunidades
sin alcantarillados, sobre todo en el centro de
la Isla. Esto me resulta en contrapunto con
lo que en su día decía Sergio Peña Cuevas,
quien fue del mismo Gabinete Ejecutivo que
mi abuelo don Luis Izquierdo-Galo, en tiempos de los Gobernadores Piñeiro y Tugwell.
Don Sergio decía: “No descansaremos hasta
que cada puertorriqueño tenga agua potable
en abundancia.” A dónde se nos fue la visión,
no sé. La traigo a la memoria histórica, para
que retomemos la visión del bien común de
nuestro pueblo, en particular dela calidad de
las aguas.
Se ha reportado que el 90% de los sistemas
individuales localizados aguas arriba de ambas represas en la Isla (Carraízo y La Plata),
no funcionan apropiadamente. Por ende, estos sistemas donde viven personas en comunidades sin alcantarillados, pueden contaminar
las represas.
La calidad del agua tiene un impacto sobre la
salud y por ende la vida familiar. Aguas contaminadas con coliformes, conducen a enfermedades gastrointestinales. Además de los
coliformes, debemos recordar la giardiasis, el
cryptosporidium y microsporidia.
La contaminación de las playas, también tiene
un efecto en la economía de la salud. El anuncio de playas contaminadas, disminuye el
turismo en la Isla. Con estas noticias, la oferta
de turismo para hacer conferencias médicas
en nuestros Centro Hoteleros, resulta menos
interesante.
Podemos mejorar en dos áreas importantes.
Primero mejorar los sistemas sanitarios. Segundo debemos mejorar el turismo médico,
dando servicios médicos a otros caribeños.
Para mejorar el sistema sanitario, primero,
tenemos que hacer inventario de lo que tenemos de infraestructura. Luego de hacer inventario de lo que tenemos en la actualidad,
hay que diseminar la información sobre la situación actual. Necesitamos hacer alianzas de
profesionales y de centros académicos con
las agencias gubernamentales para buscar y
esbozar soluciones. Finalmente, las iniciativas
para mejorar el sistema sanitario deben ser
apoyadas por los municipios y el estado. Las
soluciones han de contemplar que la infraestructura sanitaria debe variar en las diferentes
regiones de la Isla, de acuerdo a los distintos
esto contribuirá a que tengamos más médicos
acercándose a nuestras Isla, buscando conocimiento de salud y mejores servicios médicohospitalarios para sus pacientes. Finalmente,
tenemos que hacer más y mejores Congresos
para que vengan otros médicos a recibir educación médica continuada en la Isla.
eco-sistemas y regiones climáticas existentes.
Tenemos bosque tropical en el noreste, áreas
llanas y los mogotes al área central y norte,
áreas secas en el sur y áreas de estuarios.
Para mejorar el turismo médico, debemos hacer varias cosas. Primero tenemos que proyectar nuestras organizaciones médicas, como
líderes caribeños. Por otro lado, nuestros
médicos deben aceptar ser conferencistas en
las convenciones de otros países para darse
a conocer. Tenemos que resaltar el privilegio
de que en Puerto Rico tengamos una revista
médica indexada como es el Boletín. Todo
Sigamos adelante. Retomemos la visión del
Bien Común de nuestro pueblo. Estamos cercanos a una crisis hídrica. ¡Médicos despierten! Seamos líderes en el mejoramiento de
la infraestructura sanitaria.
6
Asociación Médica
de Puerto Rico
Objetivos
La Asociación Médica de Puerto Rico es fundada en el
año de 1902, cuando por aquel entonces, el insigne doctor
Manuel Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de
la colectividad y así fomentar el contínuo progreso de la ciencia y el arte de la medicina y el mejoramiento de la salud del
pueblo de Puerto Rico. Tras vencer incontables dificultades e
inconvenientes naturales de la época, se celebró la asamblea
constituyente el día 21 de septiembre de 1902, en el salón de
sesiones de la Cámara de Delegados en la iudad de San Juan.
Inscripción abierta para médicos de
Puerto Rico, USA e Islas del Caribe
Estudiantes gratis
Asóciese on-line en
www.asocmedpr.org/membresia.aspx
FARES (US dollars)
ACTIVE MEMBER
a. Not resident
b. Special member
c. Government
$ 150 $ 100 $ 60 $ 100 AFILIATE MEMBER
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$ 60
b. Resident $ 60
STUDENT
FREE
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Pago de cuota según señalado en clasificación de socios y cuotas, por medio de
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Copy of licence to practice medicine
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Enviar los documentos requeridos por correo a:
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7
Original Article/Artículos Originales
BREAST ASYMMETRY
PATTERN IN WOMEN WITH IDIOPATHIC SCOLIOSIS
Norma I. Cruz MDa*, Leo Korchin DDSa
Division of Plastic Surgery, Department of Surgery, UPR School
of Medicine, Puerto Rico Health Science Center, San Juan,
Puerto Rico.
*Corresponding author: Norma I. Cruz MD, Division of Plastic
Surgery, GPO Box 365067, San Juan, PR 00936-5067. E-mail:
[email protected]
a
ABSTRACT
Breast asymmetry is frequent in women with idiopathic scoliosis. To understand the pattern of breast asymmetry
in these women a clinical study was
performed in which 54 female patients
with idiopathic scoliosis were evaluated. The information recorded for each
patient included: age, weight, height,
scoliosis type, Cobb angle, breast measurements, and presence of rib cage
asymmetry. Breast volume was calculated using anatomic measurements
(anthropomorphic method). The mean
age of the group was 25±7 years. A right
convex thoracic curve occurred in 85%,
with a mean Cobb angle of 32±15 degrees. Our study indicated that women
with idiopathic scoliosis consistently
presented breast asymmetry that followed a predictable pattern. The breast
on the side of the convex thoracic scoliosis curve is always smaller in volume
(mean difference 59±39 ml). The affected side also presents a smaller areola,
a higher position of the nipple (mean
difference 2.2±1.3 cm) and a higher position of the inframammary fold (mean
difference 2.1±1.4 cm) when compared
to the opposite breast. Though the
asymmetry is predictable, the degree
to which the patient presents these
changes does not correlate with the severity of the scoliosis (Cobb angle). We
believe that the severity of the asymmetry is a result of the difference between
the hypoplastic breast and the normal
breasts. In women with very large opposite breasts the asymmetry appears
to be worse.
Index words: breast, asymmetry, pattern, idiopathic, scoliosis
9
INTRODUCTION
Breast asymmetry has been observed frequently in young women with idiopathic scoliosis (1,2). This type of scoliosis accounts for
80% of all cases and the cause of the condition
is unknown. It tends to run in families and may
be associated to variations of the CHD7 gene
(3-5), occurring twice as frequently in girls.
Young women with idiopathic scoliosis have
an asymmetric body development, which is not
fully understood (6). On the spine, the complex
three-dimensional deformity has two principal components; a lateral displacement of the
spine that gives it an S shape when viewed
from behind, and a rotation of the vertebrae
on their longitudinal axis. Rib cage asymmetry resulting from the vertebral rotation is also
present creating an altered rib cage curvature.
In the back this will be evident as the dorsal
hump. Less attention however, has been given
to the anterior part of the rib cage, but here a
depression will be noted on the affected side.
Breast and chest wall asymmetries in idiopathic
scoliosis have not been well studied. Asymmetries in breast mound volume, inframammary
fold position, nipple-areola complex size and
position may follow a pattern that could help
the plastic surgeon and the patient better understand the outcome of surgical procedures
aimed at correcting the problem.
PATIENTS AND METHODS
Our clinical question was: Is there a pattern of
breast asymmetry in young women who have
idiopathic scoliosis? To answer this question
an observational study collected data on 54
consecutive female patients who had idiopathic scoliosis and who were evaluated for breast
asymmetry. The information was collected
during a two-year period, starting in 2012. The
inclusion criteria for the study included being
female and having scoliosis with a Cobb angle
greater than 10 degrees (as a general rule, a
Cobb angle of 10 degrees is regarded as a
minimum angulation for defining scoliosis). Excluded from the study were women who had
secondary causes of breast asymmetry such
as previous breast or chest surgery. The Institutional Review Board of the University of
Puerto Rico approved this study and the creation of the database.
The information recorded for each patient included: age, weight, height, type of scoliosis,
Cobb angle, breast measurements, and presence of rib cage asymmetry.
The breast volume was measured be means
of the anthropomorphic method using the formula published by Qiao et al. (7-8):
Breast Volume = ⅓ πMP2 (MR+LR+IR-MP)
In this formula MR is the distance between the
nipple and the medial breast border, LR is the
distance between the nipple and the lateral
breast border, IR is the distance between the
nipple and the inframammary fold and MP is
the mammary projection, measured from sternum to nipple base in a view of the patient from
the lateral aspect. The symbol π is a numeric
constant that is equal to 3.14. All measurements are made in centimeters and are illustrated in Figure 1.
Standard breast measurements such as midclavicle to nipple distance, as well as differences in inframammary fold level and nipple level
between sides were recorded. The diameter of
the nipple-areola complex of each breast was
also measured and the difference between
sides was recorded. The same person made
all breast measurements.
All statistical calculations were made using
10
SPSS 12.0 statistical software (SPSS, Chicago, IL, USA). The difference in the breast volumes between sides was compared using the
paired t test. The correlation among the difference in volumes, nipple and inframammary
fold level and the Cobb angle were evaluated
using Pearson’s correlation analysis method.
All the data is presented as mean ± standard
deviation. Statistical significance was set at a
p value less than 0.05.
RESULTS
The mean age of our group was 25±7 years,
the mean weight was 125±21 pounds and the
mean height was 62±3 inches. A right convex
thoracic curve occurred in 85% of the group
with a mean Cobb angle of 32±15 degrees. A
left convex thoracic curve occurred in 15% of
the group with a mean Cobb angle of 35±17
degrees. Our study found that the right breast
was consistently smaller in patients with a right
thoracic curve and the left breast was consistently smaller in patients with a left thoracic
curve. The affected side not only presented
with a smaller breast volume but had a smaller
and higher nipple-areola complex and a higher
inframammary fold. The difference between
the two sides in all measurements were found
to be statistically significant (p<0.05) as shown
in Table 1. The rib cage anteriorly was always
depressed on the affected side, which worsens
the severity of the volume difference.
Pearson correlation analysis showed that the
difference in breast volume between the two
mal opposite breast. If the normal breast has
a large size the asymmetry appears to be
more severe. On the other hand, in young
women with small breasts little or no asymmetry might be noted (see Figures 2 & 3).
DISCUSSION
sides did not significantly correlate with the severity of the scoliosis as measured by the Cobb angle
(correlation coefficient r, 1.0). The other breast
measurements also had no correlation with the
Cobb angle.
The breast asymmetry of women with idiopathic
scoliosis appears to follow a pattern in which the
breast on the affected side is smaller. However,
the final breast asymmetry is a combination of the
imbalance of the hypoplastic breast with the nor-
11
Our study indicated that women with idiopathic scoliosis consistently present breast
asymmetry that follows a predictable pattern. The breast on the side of the convex
thoracic curve is always smaller in volume.
The affected side also presents a higher position of the nipple and the inframammary
fold when compared to the opposite breast,
as well as an areola of smaller diameter.
Though the asymmetry is predictable, the
degree to which the patient presents these
changes does not correlate with the severity
of the scoliosis, as measured by the Cobb
angle. The lack of correlation with the Cobb
angle has been reported previously in the literature (1,2).
We believe that the severity of the breast
asymmetry is a result of the difference between the hypoplastic breast and the normal
breast. If the normal breast has a large size
the asymmetry appears to be more severe.
On the other hand, in young women with
small breasts little or no asymmetry might
be noted. That is why we believe there is
no correlation between the severity of the
breast asymmetry and the Cobb angle.
Currently several methods are available for
measuring breast volume. Among these are
three-dimensional (3D) laser scans, nuclear
magnetic resonance imaging (MRI), computed
tomography (CT), thermoplastic casting, and
anatomic measurements (anthropomorphic
method). The MRI measurements have shown
the highest level of precision (9-11). Unfortunately, 3D laser scan, CT, and MRI are too
costly for routine assessments. We therefore
selected the anthropomorphic method as a
simple way of determining breast volume at a
low cost. The anthropomorphic equation provides a practical estimation of breast volume
with a known deviation of only 6.26% (9).
8. Tsai FC, Hsieh MS, Liao CK, Wu ST. Correlation between
scoliosis and breast asymmetry in women undergoing augmentation mammaplasty. Aesth Plast Surg 34:374-380, 2010.
9. Kovac L, Eder M, Hollweck R, et al. Comparison between
breast volume measurement using 3D surface imaging and classical techniques. Breast 16:137-145, 2007.
10. Bulstrode N, Bellamy E, Shrotria S. Breast volumen assessment: comparing five different techniques. Breast 10:117-123,
2001.
11. Kayar R, Civelek S, Cobanoglu M, et al. Five methods of
breast volume measurement: A comparative study of measurements of specimen volume in 30 mastectomy cases. Breast
Cancer: Basic and Clinical Research 5:43-52, 2011.
12. Rohrich RJ, Hartley W, Brown S. Incidence of breast and
chest wall asymmetry in breast augmentation: a retrospective
analysis of 100 patients. Plast Reconstr Surg 111:1513-1519,
2003.
Although patients with scoliosis are always afflicted to some degree by breast asymmetry, it
should be clear that patients with breast asymmetry do not necessarily experience scoliosis.
The general incidence of mild breast asymmetries has been reported in the literature to be
quite high, reaching 88% (12). To be more exact, the varying degrees of breast asymmetry
that occur include the nipple-areola complex
(24%), volume (44%), base constriction (29%),
inframammary fold position (30%), and grades
I-III ptosis (29%).
Surgeons should thoroughly evaluate breast
asymmetries, including volume as well as
nipple and inframammary fold levels preoperatively in young women who have idiopathic
scoliosis prior to breast surgery. Clear preoperative communication is crucial, so that the
patient is well informed of the risks and predicted outcome in advance. The extent of the
asymmetry very often is not clear to the patient
and unrealistic expectations may present a
problem after any plastic surgery of the breast.
REFERENCES
1. Cheung SK, Lee TK, Tse K, et al. Abnormal peri-pubertal
anthropometric measurements and growth pattern in adolescent
idiopathic scoliosis: a study of 598 patients. Spine 15:21522157, 2003.
2. Normelli H, Sevastik J, Ljung G,et al. The symmetry of
breasts in normal and scoliotic girls. Spine 11:749-752, 1986.
3.Gao X, Gordon D, Zhang D, et al. CHD7 gene polymorphisms
are associated with susceptibility to idiopathic scoliosis. Am J
Hum Genet 80:957-965, 2007.
4. Kulkarni S, Nagarajan P, Wall J, et al. Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis. Am J Med Genet A. 146A:1117-1127, 2008.
5. Tilley MK, Justice CM, Swindle K, et al. CHD7 gene polymorphisms and familial idiopathic scoliosis. Spine 2013 Jul 23 (Epub
ahead of print).
6. Hresko MT. Clinical Practice. Idiopathic scoliosis in adolescents. N Engl J Med 368:834-841, 2013.
7. Qiao Q, Zhou G, Ling Y. Breast volume measurement in
young Chinese women and clinical applications. Aesth Plast
Surg 21:362-368, 1997.
12
RESUMEN
La asimetría mamaria es frecuente en
mujeres con escoliosis idiopática. Para
tratar de comprender mejor el patrón
que siguen estas asimetrías se realizó
un estudio clínico en el cual se evaluaron 54 mujeres con escoliosis idiopática. Los datos obtenidos fueron:
edad, peso, estatura, tipo de escoliosis,
ángulo de Cobb, medidas mamarias
y presencia de asimetría de la pared
costal. El volumen mamario se calculó
usando medidas antropomórficas. La
edad media fue de 25±7 años. Presentaron con escoliosis torácica de convexidad derecha 85% de las pacientes
y el ángulo de Cobb medio fue de 32±15
grados. Nuestro estudio indica que las
mujeres con escoliosis idiopática consistentemente presentan con un patrón
de asimetrías mamarias predecibles.
La mama del lado de la convexidad de
la columna es siempre de menor volumen (diferencia media 59±39 ml). El
lado afectado también presenta con
una areola más pequeña, una posición
más alta del pezón (diferencia media de
2.2±1.3 cm) y una posición más alta del
surco submamario (diferencia media
2.1±1.4 cm) cuando se compara con el
lado contrario. Aunque la asimetría es
predecible, no encontramos una correlación con la severidad de la escoliosis
(ángulo de Cobb). Pensamos que la severidad de la asimetría depende de la
diferencia entre la mama con hipoplasia
y la mama normal. En mujeres con una
mama opuesta muy grande la asimetría
aparenta ser mayor.
Leonardo N. Catalano MDa*, Michelle Villar
Díaz MDa, Miguel Vázquez Guzmán MDa,
Ivette Negron MSa, Edgardo Rivera Rosa
MDa
Department of Obstetrics and Gynecology, San Juan City Hospital, San Juan, Puerto Rico.
*Corresponding author: Leonardo N. Catalano MD - 1663 Ave.
Ponce de Leon Apt. 505, San Juan, Puerto Rico 00909. E-mail:
[email protected]
a
13
PREGNANCY
OUTCOMES AND
SUCCESSFUL
RATE OF NIFEDIPINE
THERAPEUTIC PROTOCOL
IMPLEMENTATION IN A
HOSPITAL OF SAN JUAN
INTRODUCTION
ABSTRACT
Primary objective: evaluation of Nifedipine protocol success defined as
postponement of labor for 48 hours.
Secondary objective: evaluation of the
presence of risk factors in patients that
develop preterm labor and delivery outcome. Materials and methods: Chart review retrospective study with patients
admitted to the Hospital of the Metropolitan Area of San Juan in the period
of January 1, 2009 to December 31, 2010
with diagnosis of preterm labor. A total
of 382 patient’s records were evaluated
for inclusion and exclusion criteria. 48
met all the requirements to be included
in the study. Results: There were 68.8%
patients who successfully completed
the 48 hours postponement of labor
required to administer corticosteroid
therapy for fetal lung maturation. Risk
factors for preterm labor commonly
observed in the study group were urinary tract infection (60.4%), previous
preterm labor (43.8%), multiple gestations (12.5%), and preterm premature
rupture of membranes (10.4%). Discussion: The use of Nifedipine therapy in
patients with preterm labor between 2434 weeks of gestational age can be effective in the postponement of labor for
48 hours so that the patient can receive
corticosteroid fetal lung maturation
therapy. The most common risk factor
observed in this group of patients with
preterm labor was urinary tract infection.
Index words: pregnancy, outcomes,
nifedipine, therapeutic, protocol, implementation
Preterm labor is defined as the presence of
uterine contractions of sufficient frequency and
intensity to cause progressive effacement and
dilation of the cervix prior to full term gestation
at 37 weeks of gestational age. The preterm
birth rate increased 2% in 2004 to 12.5% of
all live births. There has been an increase to
18% in preterm births since 1990. Increases
for 2003–2004 were reported among both very
preterm births, less than 32 weeks of gestational age, and moderately preterm births, 32–
36 weeks of gestational age. Although multiple
gestations have contributed to this recent rise,
preterm birth rates for singletons have also increased, up 11% since 1990. Nearly all of the
singleton preterm rate increase is among late
preterm births 34–36 weeks of gestational age
[1]. Preterm birth is the second leading cause
of neonatal mortality in the United States, second only to birth defects. Preterm labor is the
cause of most preterm births. The ability to
predict whether a woman is going to have a
preterm delivery has a value only if an intervention is available that is likely to improve the
fetal outcome. The opportunity to administer
maternal corticosteroids therapy is an important intervention recommended by the National Institutes of Health because it is strongly
associated with a decreased in morbidity and
mortality. In addition, maternal tocolytic therapy may prolong pregnancy for up to 48 hours,
so that corticosteroids therapy for fetal lung
maturation can be administered [2]. Preterm
labor is now thought to be a syndrome initiated by multiple mechanism caused by different risk factors such as infection, inflammation,
uteroplacental ischemia, hemorrhage, uterine
over distention, stress, and other immunologically mediated process. A precise mechanism
cannot be established in most cases. In the
USA and UK women classified as black, Africa-American, and Afro-Caribbean are consistently reported to be at higher risk of preterm
delivery. Preterm birth rates are in the range
of 16-18% in black women compared to 5-9%
for white women [3]. A study done in Taiwan
evaluating risk factors for preterm labor before
34 weeks of gestational age found that odds
ratios for the largest preterm delivery risk factors were prior history of preterm labor with
16.5 OR, placental abruption 13.4 OR, prior
history of fetal death 11.8 OR, and chorioamnionitis 10.5 OR [4]. Many tocolytic drugs have
been used to inhibit preterm labor including
magnesium sulfate, β-mimetic agents, prostaglandin synthetize inhibitors and calcium channel blockers [5]. It has been demonstrated that
the use of calcium channel blockers such as
nifedipine for the treatment of preterm labor
causes a potent uterorelaxant effect, inhibitory effect on spontaneous contractions and
oxytocin-induced contraction [6]. In other study
that compares the effectiveness of β-mimetic
and magnesium chloride to no treatment, there
was no significant benefit observed in mean
gestational age, prolongation of pregnancy
and birth weight, instead potential harm was
more likely [7].
MATERIALS AND METHODS
The type of study design utilized was chart
review retrospective study. The population
evaluated was pregnant patients with the diagnosis of preterm labor (PTL) between the
ages of 14-37 years old, in the Hospital of the
Metropolitan Area of San Juan during the period of January 1, 2009 to December 31, 2010.
A total of 382 pregnant patients with diagnosis of PTL were available since the Nifedipine
protocol was implemented. Nifedipine protocol
as a tocolytic for preterm labor regimen consists of a loading dose of Nifedipine 20 mg PO,
then the maintenance dose of 10 mg PO every 4 hours. Corticosteroid used for fetal lung
maturation was Dexamethasone 6mg IM every 12 hours to complete 4 doses. A detailed
evaluation of the medical records was done
and specific information obtained included:
maternal age, gravity, parity, abortions, prenatal care, previous history of preterm birth, history of infections, preterm premature rupture
of membranes, placenta previa, past medical
history, history of tobacco use, history of alcohol use, history of illicit drug use, previous
cervical surgery, uterine malformations, psychological conditions, protocol participation,
antibiotic therapy and delivery outcome. The
inclusion criteria included: pregnant women
with an admission or discharge diagnosis of
preterm labor, gestational age range of 24-34
weeks of gestational age, pregnant women
who were enrolled in Nifedipine protocol for
tocolysis, and patients older than 14 years of
age. The exclusion criteria included: patients
younger than 14 years of age, female pregnant
patient not treated with Nifedipine as tocolytic,
female pregnant patient treated with tocolysis
other than Nifedipine, diagnosis of pregnancy
induced hypertension, pregnant patient admitted with preterm labor rush to delivery, patient
who received Nifedipine at another institution,
patient with diagnosis of Intrauterine Fetal Demise, and patient admitted with more than 34
weeks of gestational age.
RESULTS
This study was completed with the evaluation
of 382 patient’s medical records of which 48
of these patients met all the inclusion criteria. These 48 patients were pregnant women
with diagnosis of preterm labor between 24-34
weeks of gestational age that underwent treatment with Nifedipine protocol on the Hospital
of the Metropolitan Area of San Juan. The age
distribution most commonly seen was 20-24
years old with 16 (33.3%) patients, followed
by 14-19 years old with 14 (29.2%) patients
and 25-29 years old with 11 (22.9%) patients
(see Table I). Most of these patients were
multigravida 36 (75%) patients. Of the 48 patients 44 (91.7%) patients received adequate
prenatal care by an obstetrician (see Table II).
Vaginal delivery occurred in 35 (72.9%) and 13
(27.1%) patients underwent cesarean delivery.
The most common reason for cesarean section
was malpresentation in four (30.8%) patients
followed by repeat in labor in 3 (23.1%) and
non-reassuring fetal heart tracing in 3 (23.1%)
patients (see Table III). The primary goal of
treatment with Nifedipine in pregnant women
with preterm labor was to postpone labor for
at least 48 hours in order to complete corticosteroid administration for fetal lung maturation,
which was achieved in 33 (68.8%) patients
(Table IV). The correlation between weeks of
gestational age at the time of admission in
which the Nifedipine protocol was started and
the weeks of gestational age at delivery can be
seen in Table V. It can also be observed in that
table that most of these patients (20.8%) had
33 weeks of gestational age at admission and
(20.8%) patients had 33 weeks of gestational
age at delivery. At evaluation of the risk factors
present in this group of patients that can be
related to the diagnosis and outcome, the most
commonly seen were, history of preterm labor,
urinary tract infections, preterm premature
rupture of membranes, and multiple gestation.
There were 21 (43.8%) patients with history of
previous preterm labor. Out of the 33 (68.8%)
that completed tocolysis, 13 (39.4%) had a history of previous preterm labor. There were 29
(60.4%) patients with urinary tract infections.
14
Out of the 15 (31.3%) patients that did not complete tocolysis 10 (66.7%) patients had urinary tract infection.
Preterm premature rupture of membranes was observed
in 5 (10.4%) patients. Out of the 33 (68.8%) patients that
completed tocolysis, 4 (12.1%) had preterm premature
rupture of membranes. Multiple gestations were seen in 6
(12.5%) patients, 5 patients with twins and 1 patient with
triplets. Out of the 15 (31.3%) patients that did not complete tocolysis, 4 (26.7%) patients were multigestational
(see Table VI). Other risk factors for preterm labor were
not commonly observed in the study group.
DISCUSSION
The implementation and follow up of the Nifedipine protocol for pregnant women with diagnosis of preterm labor
between 24-34 weeks of gestational age in the Hospital
of the Metropolitan area of San Juan demonstrated to be
an effective tocolytic treatment for postponement of labor
for at least 48 hours so that the administration of corticosteroid treatment for fetal lung maturation could be completed. The successful completion of this therapy can improve the fetal outcome as demonstrated in other studies.
Among the risk factors for preterm labor observed in this
study, the most common one was urinary tract infection
in 60.4% of patients followed by previous preterm labor
in 43.8% of patients. Other risk factors for preterm labor
were not so common in this group.
Nifedipine is one of the most common used tocolytic
agent with benefits showed in multiple research studies. Some of the limitations of this study include a small
sample available, lack of medical records available of
previous pregnancies and no control group to compare
outcomes. The proper implementation of this and other
evidence based protocols that can improve the outcome
Table V. Gestational Age Distribution
15
of the patients should be considered in similar
settings. Further studies can be done to compare the effectiveness of this protocol to other
tocolytic drugs. As seen in this study, some
of the risk factors such as urinary tract infections can be detected earlier with early and
adequate prenatal care, and treatment can be
started to decrease the risks of preterm labor.
ACKNOWLEDGMENT
Josefina Romaguera MD for manuscript research assistance & Gustavo Vazquez Zweig,
for literature research assistance.
REFERENCES
1.
Martin JA, Hamilton BE, Sutton PD, et al. Birth: Final
data for 2004. Natl Vital Stat Rep 2006; 55(1):1-101.
2.
Prediction and prevention of preterm birth. Practice
Bulletin No. 130. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012; 120:964-73.
3.
Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet Jan 5, 2008;
371(9606):75-84.
4.
Chung-Chin L, Jenn-Jeih H, Ching-Chang H, T’sangT’ang H, Tai-Ho H.
Risk Factors for Spontaneous Preterm Delivery Before 34
Weeks of Gestation Among Taiwanese Women. Taiwan J Obstet
Gynecol 2007; 46:389-394.
5.
Ables AZ, Romero AM, Chauhan SP. Use of calcium
channel antagonist for preterm labor. Ostetrics and Gynecology
Clin N Am 2005; 32:519-525.
6.
Moynhihan AT, Smith TJ, Morrison JJ. The relaxant effect
of nifedipine in
human uterine smooth muscle and BKCa channel. American
Journal of Obstetrics and Gynecology 2008; 198:237.e1-237.e8.
7. Berckman ND, Thorp JM, Lohr KN, et al. Tocolytic
treatment for the
management of preterm labor: A review of the evidence. Am J
Obstet Gynecol 2003; 188:1648-59.
RESUMEN
Objetivo primario: evaluación del éxito obtenido con protocolo de Nifedipina definido como
la prolongación del trabajo de parto por 48 horas. Secundario: evaluación de factores de
riesgo presentes en pacientes que desarrollaron parto prematuro y su resultado. Materiales y Métodos: Se hizo un estudio retrospectivo de revisión de los expedientes médicos de
pacientes admitidas al Hospital del Área Metropolitana de San Juan durante el periodo del
1 de enero del 2009 hasta el 31 de diciembre del 2010 con el diagnostico de parto prematuro. Un total de 382 records médicos fueron evaluados en cuanto a criterios de inclusión y
exclusión, en donde 48 de estos cumplían con todos los requisitos para ser incluidos en el
estudio. Resultados: Hubo 68.8% de pacientes que completaron exitosamente las 48 horas
de prolongación de labor requeridas para la administración de terapia con esteroides para
la maduración pulmonar fetal. Los factores de riesgo para parto prematuro mas observados
en el grupo de estudio fueron infección de orina (60.4%), parto prematuro previo (43.8%),
embarazos múltiples (12.5%), y ruptura de membranas prematura (10.4%). Discusión: El
uso de Nifedipina en pacientes con parto prematuro entre las 24-34 semanas de gestación
puede ser efectivo en la prolongación de la labor del parto por 48 horas de modo que la
paciente pueda recibir terapia con esteroides para la maduración pulmonar del feto. El factor de riesgo mas común observado en este grupo de pacientes con parto prematuro fue
infección de tracto urinario.
16
La AMPR concentrará parte de sus esfuerzos en la
educación en informática de salud e investigación
y mejoramiento de las técnicas médicas, como
parte de su programa anual de educación médica
continua.
Manténgase informado.
Wilma González BSa, Pablo I. Altieri MDab*,
Silo Alvarado MSIIa, Héctor L. Banchs MDa,b,
Nelson Escobales PhDa, María Crespo
PhDa, William Borges MDa
MAGNESIUM:
The Forgotten
Electrolyte
17
Department of Medicine and Physiology, UPR School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico.
Cardiovascular Center of Puerto Rico and the Caribbean, San
Juan, Puerto Rico.
*Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: [email protected]
a
b
INTRODUCTION
ABSTRACT
Magnesium (Mg++), Potassium (K+)
and Calcium (CA++) are important
electrolytes in keeping a stable electrical status. The purpose of this study
was to measure them in critically ill
patients. Methods: We evaluated the
electrolytes in 28 consecutive patients.
Eighteen were females and 10 males
with mean age of 62 ± 5 years. Results:
The admission diagnosis in 95% of the
cases was congestive heart failure.
Sixty-four percent of the patients had
subnormal values of Mg++, 53% subnormal values of K+, and 28% subnormal values of CA++. Fourteen percent
showed lower values of the three electrolytes and 35% only of Mg++ and K+
concomitantly. Twenty-eight percent
showed prolonged QTC interval. All
patients with prolonged QTC interval
had low Mg++ and K+ levels. Twentyfive percent of the patients showed
atrial fibrillation, 25% ventricular tachycardia, and 3% junctional tachycardia.
The ventricular tachycardia group had
more electrolyte abnormalities than
those with atrial fibrillation. None of the
patients received Mg++ replacement
during critical management while 50%
received K+ replacement. Conclusion:
This data shows physician overlook the
importance of Mg++ and K+ deficiency
in critically ill patients.
Index words: magnesium, forgotten,
electrolyte
Patients with severe Congestive Heart Failure
(CHF) usually demonstrate severe disturbances of acid-base and electrolytes concentrations.1,2 The electric system of the heart could
be affected by electrolyte disorders causing
abnormalities on cardiac ionic current kinetics,
promoting proarrhythmic effects.4,5 Magnesium
(Mg++), calcium (CA++) and potassium (K+)
maintain a correlation that regulates the ionic
channels4,5 These concentrations are essential
for proteins and nucleic acids synthesis, and for
internal metabolism and myocardial function6.
In collaboration with CA++ and K+, Mg++, the
fourth most abundant ion in the body, has a
big influence on cardiac arrhythmias by maintaining normal intracellular concentrations of
K+ 2,3. Critically ill patients usually show an increase incidence of arrhythmias, which could
lead to fatal consequences. It is the purpose
to analyze the electrolyte balance in a group of
patients hospitalized at the Intensive Care Unit
of our institution to find out the correlation between electrolyte in balance and arrhythmias
and the protocol of replacement if deficiencies
are found.
MATERIAL AND METHODS
The study consists of twenty-eight patients admitted to the Intensive Care Unit of the Cardiovascular Center of Puerto Rico due to different
medical conditions (see Table 1). The patients
were submitted to standardized tests which included primary diagnosis, mass index, cholesterol, blood pressure, electrolytes concentrations, a 12-lead electrocardiogram and other
diagnostic tests. Automated QTC interval was
calculated in all cases. Replacement therapy
for electrolyte abnormalities was analyzed.
RESULTS
We evaluated 28 consecutive critically ill patients with a mean age of 62±5 years. 64%
were men and 18% were women with an admission diagnosis of CHF (95%). Acute myo-
cardial infarction (AMI) occurred in 5% with its
attendant complications. All patients suffered
from arterial hypertension, 89% had diabetes
mellitus and 35% chronic kidney disease. The
clinical demographic characteristic of the patients is shown in Table 1.
Sixty-four percent of the patients were females
and 36% males with a mean age of 62 years.
64% of the patients had subnormal values of
Mg++ < 2mg% (1.8 ± 0.2mg%); 53% subnormal values of K+ < 4.0mg% (3.8 ± 0.7mg%) and
28% subnormal values of CA++ < 8mg% (7.4 ±
0.1mg%). Fourteen percent showed lower values of the three electrolytes and 35% only of
Mg++ and K+ combined. Twenty-eight percentshowed prolonged QTC interval > 440 msec
(511 ± 32 msec). All patients with prolonged
QTC interval had low Mg++ and K+ levels.
Four patients had atrial fibrillation, 2 ventricular tachycardia and one junctional tachycardia.
Twenty-five percent of all the patients showed
atrial fibrillation, 25% ventricular tachycardia,
and 3% junctional tachycardia. All the patients
with atrial fibrillation had electrolyte abnormalities, mostly low Mg++ and K+ combined, while
only one of the ventricular tachycardia showed
normal electrolytes, the others a combination
of electrolyte abnormalities.
The ventricular tachycardia group had more
electrolyte abnormalities than those with atrial
fibrillation. Table 2 shows a summary of the
electrolyte abnormalities. None of the patients
received Mg++ replacement while in management, while 50% received K+ replacement.
DISCUSSION
Mg++, K+ and CA++ electrolytes have an important role in regulating the electrical and
muscle systems of the heart. The result of this
study shows that subnormal values of these
electrolytes have an important role in the
production of atrial fibrillation and ventricular
tachycardia. It is known that the incidence of
arrhythmias increases by 50% when an abnormality occurs in these electrolytes3,4,8. This was
seen in our critically ill patients. When low values of theses electrolytes were not corrected,
these arrhythmias were induced in critical moments of their disease.
Several investigators1-34 have described several factors in the Mg++ -K+- CA++ relationship.
Their clinical importance in different clinical
environments has prompted listed mechanism
why these electrolytes abnormalities produce
arrhythmias. Some of the different theories include:
1. Mg++ deficiency can contribute to cardiovascular damage and to functional abnormalities.
2. Mg++ deficiency interferes with K+ retention,
so that Mg++ protects against K+ loss. This is
related to the Na+ and K+ pump exchange for
H+. Alteration in the function of this pump in
the setting of low Mg++ may affect myocardial
excitability.
3. There are CA++ shifts in Mg++ deficiency.
4. The arrythmogenic potential of Mg++ deficiency can be related to imbalance between
Mg++ and K+ or between CA++ or both.
5. The loss of myocardial K+ that results from
Mg++ loss predisposes to arterial and coronary
spasm and increase in catecholamine release.
6. The most common cause of Mg++ deficiency is loop diuretics like furosemide.
7. Mg++ deficiency increases the Lanoxin ef-
18
fects, lowering the threshold for Lanoxin induced arrhythmia, especially in ventricular
tachycardia.
8. Low Mg++ increases sinus node automaticity producing supraventricular arrhythmias.
All these observations discussed by Seilig9
shows the importance of keeping a normal
Mg++, K+ and CA++ levels in critically ill patients to avoid the high incidence of atrial fibrillation and ventricular tachycardia in this critical
period.
Mg++ and K+ deficiency frequently exist in
these critically ill patients. Low levels of Mg++
have been shown to potentiate the electrophysiological effect of hypokalemia increasing
the incidence of atrial fibrillation and ventricular tachycardia. This relationship in chronically
ill patients is not known, but is clear that low
Mg++ and low K+ induces atrial fibrillation and
ventricular tachycardia. Algandi and Kohnas
had shown the importance of the Mg++ infusion in the reduction post-operative of both arrhythmias13-14. Khan34 showed that low serum
Mg++ is common in the general population.
Also, it is interesting that prolongation of the
QTC interval shown in some of our patients
in an ECG has been established and related
to abnormalities pathognomonic of electrolyte
disturbances that lead to risk for development
of fatal cardiac arrhythmias, especially ventricular tachycardia. Zhang25 found association
between abnormal prolongation of QTC interval with mortality and sudden death. This prolongation may occur in association with drugs,
lacking an adequate nutrition and diuretic loop,
lowering the serum levels of Mg++ and K+.
Mcbride32, showed QTC reductions with oral
Mg++ solutions demonstrating the importance
of Mg++ on the corrected QTC interval of ill patients.
Complications in our patients could be related
to Mg++ and K+ levels in serum. The most frequent drug used was furosemide that reduces
the serum levels of both electrolytes and prior to
admission no drug that increased QTC interval
was being used. None of the patients received
Mg++ supplement and only 50% received K+
supplements. Our results are in accordance
with previous studies which demonstrate that
most ill patients in Intensive Care Unit does do
not receive adequate electrolyte replacement,
especially for Mg++, increasing the risk for
arrhythmias. This also shows that we should
have strict rules and protocols in dealing with
these electrolyte problems, because if not, the
life of patients will be compromised.
CONCLUSION
Complications with patients could be highly
related to Mg++ deficiency that is rarely considered in clinical practice. The most frequent
drug used was furosemide and prior to admission no drug was being used which could increase QTC interval. None of the ill patients
received Mg++ replacement and 50% received
K+ replacement. Our results are in accordance
with previous studies that demonstrate that
most of the ill patients on intensive care do not
receive adequate electrolytes concentrations,
especially for Mg++, increasing the risk of arrhythmias and its complications. By this form,
our study should stimulate future interest in
Mg++ as a therapeutic strategy for treatments
of arrhythmias for ill patients.
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(28) Raehl C. L., Patel, A. K., LeRoy, M. (1985). Drug-induced
torsade de pointes. Clin Pharm. 4(6): 675-90.
(29) Yalta, K., Turgut, O., Yilmaz, A., Yilmaz M. B., Kendirlioglu,
O., Karadas, F. (2007). Torsades de pointes with a severly prolonged QT interval induced by an initial low dose sotalol intake.
Int J Cardiol. 116(3): e95-7.
(30) Picard, S., Lacroix, P. (2003). QT interval prolongation and
cardiac risk assessment for novel drugs. Curr Opin Investig
Drugs. 4(3): 303-8.
(31) Pasquier, M., Pantet, O., Hugli, O., Pruvot, E., Buclin, T.,
Waeber, G., Aujesky, D. (2011). Prevalence and Determinants
of QT Interval Prolongation in Medical Inpatients. Intern Med J.
42(8): 933-40
(32) McBride, B. F., Min, B., Kluger, J., Guertin, D., Henyan, N.
N., Coleman, C. I., Silver, B.B., White, C.M. (2006). An evaluation of the impact of oral magnesium lactate on the corrected
QT interval of patients receiving sotalol or dofetilide to prevent
atrial or ventricular tachyarrhythmia recurrence. Ann Noninvasive Electrocardiol. 11(2): 163-9.
(33) Van Noord, C., Straus, S. M., Sturkenboom, M. C., Hofman,
A., Aarnoudse, A. J., bagnardi, V., Kors, J. A., Newton-Cheh, C.,
Witteman, j. C., Stricker, B. H. (2009). Psychotropic drugs associated with corrected QT interval prolongation. J Clin Psychopharmacol. 29(1): 9-15.
(34) Khan AM, Lubitz SA, Sullivan LM, Sun JX, Leby D, et al.
Low Serum Magnesium and Development of Atrial Fibrillation in
the Community- The Framingham Heart Study. Circulation 2013;
127:33-38.
20
RESUMEN
Magnesio (Mg++), potasio (K+) y calcio
(CA++) son importantes en mantener un
estado electrofisiológico estable. Estudiamos los niveles en suero de estos
electrolitos en pacientes críticamente
enfermos. Método: veintiocho pacientes críticamente enfermos fueron estudiados. Diez y ocho eran mujeres y 10
hombres con una edad promedio de 62
± 5 años. Resultados: El diagnostico
de admisión de 95% de los casos fue
fallo congestivo del corazón. Sesenta y
cuatro porciento de los pacientes tuvo
valores subnormales de Mg++, 53%
valores subnormales de K+, y 28% valores subnormales de CA++. Catorce
porciento tuvo valores bajos de los tres
electrolitos y 35% solo de Mg++ y K+
combinados. Veinte y ocho porciento
tuvo un intervalo QTC prolongado. Todos los pacientes con QTC prolongado
tenían niveles bajos de Mg++ y K+. 25%
de los pacientes tuvo fibrilación atrial
25% taquicardia ventricular y 3% taquicardia de juntura. El grupo con taquicardia ventricular tuvo mas disturbios
electrolíticos que aquellos con fibrilación atrial. Ninguno de los pacientes
afectados recibió remplazo de Mg++
cuando estaba en tratamiento critico
mientras 50% recibieron remplazo de
K+. Conclusión: Esta data muestra que
los médicos pasan por alto la importancia de deficiencias de Mg++ y K+ en pacientes críticamente enfermos.
COMPARISON OF THE APPROPRIATE USE OF
ANTIBIOTICS BASED ON CLINICAL GUIDELINES
BETWEEN PHYSICIANS IN-TRAINING VERSUS
PRACTICING PHYSICIANS
Francisco Fernández González MDa*,
Javieth Detrés MDa, Pedro Torrellas MDa,
Carmen R. Balleste MDb
21
Internal Medicine Department, San Juan City Hospital, San
Juan Puerto Rico. bInfectious Diseases Department, San Juan
City Hospital, San Juan Puerto Rico.
*Corresponding author: Francisco Fernández-González MD Street 311 Teresa Jornet, Cond. Tropical Courts, Apt. 202, San
Juan, Puerto Rico 00996. Email: [email protected]
This research participated as a poster presentation at the PR
ACP 2012.
a
ABSTRACT
The inappropriate antibiotic can lead to serious negative effects on health. This has
been the cause of emergence of multidrug resistant bacteria and the need of surveillance of antibiotics in the inpatient setting. An adequate knowledge on which and
when prescribing antibiotics is essential to avoid these issues. Because of this problems, guidelines have been developed to educate and control the misuse and abuse
of antibiotics and improve clinical outcomes. We evaluated the medical knowledge,
medical trends, and the effectiveness of professional interventions among Puerto
Rico physicians in promoting prudent antibiotic prescribing. A comparative study
was performed using a questionnaire about prudent antibiotic use in common infections seen in Puerto Rico. It was distributed among the major three internal medicine
training programs at San Juan, internal medicine physicians and general physicians.
General physicians failed to treat adequately asymptomatic bacteriuria, and overall
failed in treating other common conditions when compared with residents and internal medicine physicians. One of our questions was related to the treatment of Extended Spectrum Beta Lactamase (ESBL) positive Escherichia coli (E. coli) and more
than 50% of the surveyed failed to answer the question correctly. Conditions as viral
respiratory tract infections and community acquired pneumonia had the higher correctly answered questions among the groups. Our questionnaire demonstrates that
guidelines have to reach the education among the general physician population to
decrease the overuse of inadequate antibiotics, and education should be strengthen
on those internal medicine physicians that have already completed formal training.
Index words: comparison, appropriate, antibiotics, clinical, guidelines, physician,
in-training
INTRODUCTION
a process called transformation.
The inappropriate antibiotic use is the overuse
or misuse of antibiotics commonly seen in the
hospital setting and outpatient. It creates multidrug resistant bacteria and life-threatening infections (1). While sensitive bacteria are killed,
resistant microbes may be left to grow and
multiply. There are several mechanism for bacteria to acquire resistance for antibiotics such
as the process of conjugation in which a genetic material (a plasmid containing the genes
for resistance for a particular antibiotic) is
transferred to another bacteria. In addition, as
bacteria becomes competitive, they can also
acquire genetic material from its sorrounding,
As resistance towards antibiotics becomes
more common, a greater need for alternative
treatments arises. However, despite a rush
for new antibiotic therapies there has been a
continued decline in the number of newly approved drugs (2). The consequences include
prolonged illnesses, more doctor visits or extended hospital stays, and the need for more
expensive and toxic medications. Multiple factors may influence this problem. Cultural factors determine which sign and symptoms are
perceived as abnormal and thus require medical care and drug treatment (3). The pediatric
patients are the most common affected popu-
lation from the misuse of antibiotics, probably
due to parent pressure. In a study by Mangione
et al showed that doctors prescribe antibiotics
62% of the time if they perceive parents expect
them and 7% of the time if they feel parents do
not expect them (4).
In a study conducted by Cadieux et al, concluded that International medical graduates,
physicians with high-volume practices and
those who were in practice longer were more
likely to prescribe antibiotics inappropriately
(5). Therefore, some modalities to reduce antimicrobial resistance should take place. In the
45th Annual Meeting of Infectious Diseases,
Louis Rice delivered the Maxwell Finland Lecture and concluded that reduction length of antibiotic courses was the antibiotic use strategy
most likely to be effective in reducing resistance (6).
METHODS
A comparative study using a questionnaire
(see questionnaire in the attachment) about
the prudent antibiotic use in common infections
seen outpatient as well as inpatient in Puerto
Rico was fashioned. This questionnaire was
based in guidelines from Infectious Diseases
Society of America (IDSA) and CDC. The Institution Review Board approved this research.
The questionnaire for physicians had fourteen
questions based on daily living condition that
you could treat as in patient or outpatient. The
questionnaire seeks what are the trends in prescription according to certain conditions mostly
based on clinical guidelines. The questionnaire
takes about 20-30 minutes to be completed
and is not a test. It was anonymous. All questions have four options.
The misuse of antibiotics has lead to negative
economic impact worldwide. In the US $1.1 billion is spent annually on unnecessary adult upper respiratory infection antibiotic prescriptions
(7). National Ambulatory Medical Care Survey
(NAMCS) data shows that overall antibiotic
prescribing dropped from 13.8 prescriptions
per 100 office visits to 12.0 prescriptions per
100 office visits comparing 1997-98 to 200506 with a 13% reduction in overall antimicrobial prescribing (8). Due to these problems, the
Center for Disease Control created programs
such as the Antibiotic Stewardship in order to
improve the administration of antibiotics, to
ensure cost-effective therapy as well as to improve morbidity. The number of prescriptions
continues alarming, posing a risk for more
multi-drug resistant pathogens.
Inclusion Criteria
The objectivo of this work was to evaluate the
effectiveness of professional interventions
among Puerto Rican physicians in promoting
prudent antibiotic prescribing and how it varies
according to years in practice, education and
clinical experience. The goal is to obtain information on what physicians are doing in their
daily practice and if the decisions made are
based in the guidelines for disease established
that are now accessible through Internet. We
want to identify which group prescribes antibiotics with adequate coverage for conditions
and if they consider microbiology and cost in
their decisions. In addition, we want to compare if the knowledge of guidelines is greater
between residents versus internal medicine
practitioners versus general physicians.
Questionnaire will not be completed by attending physicians.
Medical students.
Questionnaire not based on pediatric or pregnant patients.
Non active physicians or retired.
Questionnaire to be completed by Internal
Medicine active residents from San Juan City
Hospital, University Hospital of Puerto Rico,
and Veteran Affairs Caribbean Healthcare
System. This includes fifteen residents from
each hospital mentioned.
Fifteen General practitioner physicians randomly selected from any hospital or clinics in
Puerto Rico.
Fifteen Internal Medicine physicians (regardless of their ages) selected from any hospital
or clinics in Puerto Rico.
All participant from both sexes.
Questionnaire based only on adult patients
Exclusion Criteria
For results refer to Figure 1 and 2.
DISCUSSION
Questionnaires were completed by 15 members of each of the study groups. A total of 75
individuals participated int the questionnaire.
We found that residents and Internal medicine
physicians gave more accurate answers than
general practitioner physicians. General physicians failed to treat adequately asymptomatic
bacteriuria, and overall failed in treating other
22
23
common conditions when compared with residents and internal medicine physicians.
Since Dengue fever is a common condition
seen in Puerto Rico and efforts of the CDC
has been implemented to keep all physicians
being alert and treating dengue adequately,
both residents and general physicians identified and treated dengue adequately with 100%
of questions answered correctly. Developing
of bacterial resistance and the use of the adequate antibiotic for the adequate bacteria is
one of the major concerns among Infectious
Diseases specialists.
One of our questions was related to the treatment of ESBL positive E. coli and more than
50% of the surveyed failed to answer the question correctly. Conditions as viral URTI (upper
respiratory tract infections) and CAP (community acquired pneumonia) had the higher correctly answered questions among the groups
that correlate with the emphases that is given
in treating this conditions by means of continued medical education, core measures and
more frequent patient care.
Our questionnaire demonstrated that guidelines have to reach the education among general physician population to decrease the overuse of inadequate antibiotics, and education
should be strengthen on those internal medicine physicians that have already completed
formal training.
The antibiotic Stewardship Program must be
followed by all hospitals in Puerto Rico in order
to reach better outcomes in our patients.
REFERENCES
1) Harrison JW, Svec TA (April 1998). "The beginning of the end
of the antibiotic era? Part II. Proposed solutions to antibiotic
abuse". Quintessence International 29 (4): 223–9.
2) Donadio, Stefano; Maffioli, Sonia; Monciardini, Paolo; Sosio,
Margherita; Jabes, Daniela (August 2010). "Antibiotic discovery
in the twenty-first century: Current trends and future perspectives". The Journal of Antibiotics 63 (8): 423–430.
3) de Melker RA, Touw-Otten FW, Kuyvenhoven MM. Transcultural differences in illness behaviour and clinical outcome:
an underestimated aspect of general practice? Fam Pract.
1997;14:472–7.
4) Mangione-Smith R, McGlynn EA, Elliott MN, et al: The relationship between perceived parental expectations and pediatrician antimicrobial prescribing behavior. Pediatrics 103:711-718,
1999.
5) Cadieux G, Tamblyn R, Dauphinee D. Predictors of inappropriate antibiotic prescribing among primary care physicians.
CMAJ. 2007 Oct 9;177(8):877-83.
6) Rice LB. The Maxwell Finland lecture: for the duration—rational antibiotic administration in an Era of antimicrobial resistance
and Clostridium difficile. Clin Infect Dis 2008; 46:491–6.
7) Fendrick AM, Monto AS, Nightengale B, Sarnes M: The economic burden of non-influenza related viral respiratory tract infection in the United States. Arch Int Med: 163(4): 487-94, 2003.
8) National Ambulatory Medical Care Survey (NAMCS).
24
RESUMEN
El uso inadecuado de antibióticos nos
puede llevar a serios efectos negativos
para la salud. Esto ha sido la causa
emergente de la aparición de bacterias
multiresistentes y de la necesidad en la
búsqueda de nuevos antibióticos en el
ambiente hospitalario. El conocimiento
adecuado para cuando y a quién prescribir antibióticos es esencial para
evitar estos problemas. Debido a estos
problemas, guías se han establecido
para educar y para evitar el abuso y
mal uso de antibióticos y mejoría clínica. Por tal razón, nosotros evaluamos
el conocimiento medico, tendencias
médicas y la efectividad de intervenciones profesionales entre médicos de
Puerto Rico en promover la prescripción adecuada de antibióticos. Un estudio comparativo fue realizado utilizando
un cuestionario sobre el uso adecuado
de antibióticos en infecciones comúnmente vistas en Puerto Rico. Este fue
distribuido entre tres programas principales de entrenamiento de medicina interna en San Juan, médicos internistas
y médicos generalistas de Puerto Rico.
Los médicos generalistas fracasaron
en tratar adecuadamente la bacteriuria
asintomática y en promedio, fracasaron
en tratar otras condiciones comunes
cuando se compararon con residentes
y médicos de medicina interna. Una de
nuestras preguntas fue relacionada al
tratamiento de ‘Escherichia coli’ betalactamasa de espectro extendido y más
del 50% del los participantes fracasaron en contestar la pregunta correctamente. Condiciones tales como infecciones de tracto respiratorio superior
y pulmonía adquirida en la comunidad
tuvieron la puntuación mas alta entre
todos los grupos. Nuestro cuestionario demostró que las guías necesitan alcanzar la educación entre la población de médicos generalistas para
disminuir el sobreuso de antibióticos,
y la educación se debe de fortalecer
en aquellos médicos internistas que ya
han completado un entrenamiento formal.
PREGNANCY AND NEONATAL OUTCOMES OF
WOMEN RECEIVING COMPOUNDED 17- α
HYDROXYPROGESTERONE AT SAN JUAN CITY
HOSPITAL
Olga M. Pereira MDa*, Soan G. Cruz Ortiz
MDa, Amaury Llorens MDa, Edgardo Rivera
Rosa MDa
Department of Obstetrics and Gynecology, San Juan City Hospital, San Juan, Puerto Rico.
*Corresponding author: Olga M. Pereira MD – P.O. BOX 7206,
Ponce, Puerto Rico 00732. E-mail: [email protected]
a
ABSTRACT
Objective: To describe the pregnancy
and neonatal outcomes of women receiving 17α-hydroxyprogesterone to
prevent subsequent preterm birth in our
institution. Methods: Forty-two patients
received treatment by VITA healthcare
and their charts were reviewed for results and outcomes. Results: An increase in average gestational age at
the time of delivery was noticed as well
as an increase in weeks gained compared to previous preterm birth. Discussion: More than 75% of the patients
prolonged their pregnancy with the use
of 17α-hydroxyprogesterone. Continuation of the study and stratifying patients will help in identifying other risk
factors and establishing criteria for improved prevention of preterm birth and
prognosis.
Index words: pregnancy, neonatal, outcome, women, hydroxyprogesterone,
San Juan, hospital
INTRODUCTION
Preterm birth (PTB) is the leading cause of
neonatal mortality and the most common reason for antenatal hospitalization. In the United
States approximately 12% of all live births occur before term, and preterm labor preceded
approximately 50% of these preterm births as
of 2012 (1). In the United States the rate of PTB
in Hispanics is 12%. In Puerto Rico, the most
recent statistics recognized the rate of preterm
25
birth to be higher, about 17.6% (see Figure 1).
There is increasing evidence that progesterone
supplementation can reduce the rate of PTB
in high-risk women. 17α-hydroxyprogesterone
(17HP) has been used since the 1970’s for
prevention of preterm labor (2). Over many
decades, despite several randomized trials,
conflicting evidence has resulted in limited
use in clinical practice. The inclusion of mixed
populations such as women with recurrent
pregnancy loss and those presenting with active preterm labor might explain the conflicting
evidence (3,4). Additionally, some trials included only small number of patients. In 1990,
a meta-analysis of seven placebo-controlled
trials involving prophylactic 17HP found that
the use of this agent was associated with a
15-70% reduction in occurrence of preterm
birth, but no significant reduction in perinatal
mortality, morbidity, or miscarriage (5,6). The
American College of Obstetrics and Gynecologist recommend 17α-hydroxyprogesterone for
the prevention of preterm labor in selected patients (1,6-8). The criteria for 17HP use include
women with previous history of a spontaneous
singleton preterm birth at less than 37 weeks
of gestation. Although there are multiple studies revealing the incidence and preterm birth
outcomes in the United States, little is known
about these in the Puerto Rico’s population.
The objective of this observational study was
to identify the maternal and neonatal outcomes
after 17α-hydroxyprogesterone administration
in Hispanics patients who met the criteria for its
use at the San Juan City Hospital.
MATERIALS AND METHODS
This observational study includes 42 female
patients with prior history of one or more spontaneous preterm birth at San Juan City Hospital from 2010-2012 (see Figure 2). Patients
who met the criteria for intramuscular (IM)
17α-hydroxyprogsterone (17HP) were identified at prenatal care clinics. The protocol for
prevention of PTB with 17HP by VITA healthcare was introduced in 2009-2010 at our institution. The patients at risk were referred to
VITA healthcare service. The program provides
home nursing services for the administration of
the injection and adequate follow up. Patients
received IM 17HP weekly from sixteen weeks
of gestation until 36 weeks or delivery, as es-
tablished by American College of Obstetric and
Gynecology. The home nursing program charted the information regarding patient’s history,
gestational age at the beginning of treatment,
dates when treatment was discontinued, Apgar
score, baby’s weight, admission to the neonatal intensive care unit and gestational week
upon delivery. The charts were studied contemplating the patients treated since 2010 until
2012. The data taken into consideration were:
recurrent spontaneous preterm birth, mean interval of weeks gained, baby’s weight, NICU
admission and average gestational age at time
of delivery. Our study consists of a description
of patient’s results after receiving 17HP over a
period of time. We identify the characteristics
of the particular group of patients with previous preterm birth who were candidates for
17HP and their subsequent course throughout
pregnancy. The Ethics Committee of the San
Juan City Hospital in San Juan, Puerto Rico,
approved the study.
RESULTS
From 2010-2012 forty-two patients were
referred to VITA healthcare to receive
17α-hydroxyprogesterone weekly starting
as early as 16 weeks gestational age (GA)
through 36 weeks GA or delivery. The following
means and percentages were calculated using
the data collected from the patient’s charts at
the home nursing program. To describe some
demographic information 38% of the patients
resided outside the San Juan area, the remainder 62% lived in the San Juan area (see
Figure 2). The 17HP program by VITA healthcare identified that 48% of the population received the current government health insurance (see Figure 3). The average gestational
age at which patients began treatment was at
21.6 weeks of gestation. The mean gestational
age at which patients delivered or went into labor was 36.5 weeks (see Figure 4). Also, mean
gestational age of previous preterm birth was
calculated to be 29.8 weeks. Based on these
findings, the interval of weeks gained, comparing previous preterm birth gestational age with
the current GA at delivery was 7 weeks. The
76.2% of patients in the observational group
prolonged their pregnancy for an average of 7
weeks (see Figure 5). The remainder groups
were divided in stillbirths (4.8%), no gain or delivery at same gestational age (2.4%) and incomplete charts (16.6%). The range of weeks
gained in our population was from 1.8 weeks
to 22 weeks. Forty percent of patients had history of more than one previous preterm birth,
60% of patients had only one prior PTB. When
evaluating neonatal outcomes a 4.8% reported
stillbirths (2 patients with perinatal death between 22-25 weeks GA). Admissions to the
26
27
Neonatal Intensive Care Unit (NICU) were
seen in 11.9% of cases. Of these NICU admissions, 40% were reported to be associated
with respiratory problems; 20% associated to
infectious process; 20% were described as
complications from prematurity and the other
20% were from unspecified causes. The average stay at the NICU was seven days. Other
outcomes could not be evaluated due to incomplete charts or patient’s failure to follow-up
after delivery.
DISCUSSION
The use of 17α-hydroxyprogesterone is clinically proven to decrease preterm birth among
women with prior history of preterm birth. Its
etiology is still unknown but the impact of its
use is valuable. The most important result in
our study is the effective prolongation of gestation in a subsequent pregnancy for an average
of 7 more weeks, compared to previous preterm birth gestational age (refer to Figure 5).
Our analysis relates to other studies performed
before,
which
confirms
that
17α-hydroxyprogesterone use decrease significantly the recurrence of preterm birth and
prolongs subsequent pregnancy. The study
is an observational one, where patients were
evaluated over a period of time. The data collected was analyzed and results from observation are presented here.
www.marchofdimes.com/peristats Retrieved May 24, 2013
3. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B,
Moawad AH, et al. Prevention of recurrent preterm delivery by
17 alpha-hydroxyprogesterone caproate. National Institute of
Child Health and Human Development Maternal-Fetal Medicine
Units Network. N Engl J Med 2003; 328:2379-85.
4. Spong CY. Prediction and prevention of recurrent spontaneous preterm birth. Obstet Gybecol 2007;110:405-15.
5. Hayworth SD, Bernstein P. Preventing Preterm Birth; The
Role of 17P. ACOG, Task Force and March of Dimes. Jan 2009
6. Simhan NH, Iams JD, Romero R. Preterm birth. In: Gabbe
SG, Niebyl JR, Simpson JL, Landon MB, Galan HL, Jauniaux
ER, et al, editors. Obstetrics: normal and problem pregnancies.
6th ed. Philadelphia (PA): Elsevier Saunders; 2012;628–56.
7. Preterm singleton births--United States, 1989-1996. Centers
for Disease Control and Prevention (CDC). MMWR Morb Mortal
Wkly Rep 1999;48:185–9.
8. Petrini JR, Calaghan WM, Klebanoff M, et al. Estimated effect
of 17 α-hydroxyprogesterone caproate on preterm birth in the
United States. Obstet Gynecol, 2005; 105(2):267-72
9. Joy S, Rhea Dj, Istwan NB, et al. The risk for preterm labor in
women receiving 17 α-hydroxyprogesterone caproate prophylaxis for preterm birth prevention. Am J Perinatol, 2010; 27(4):
343-8. doi:10.1055/-0029-1243306
10. Sibai BM, Istwan NB, Palmer B, Stanziano GJ. Pregnancy outcomes of women receiving compounded
17α-hydroxyprogesterone caproate for prophylactic prevention
of preterm birth 2004-2011. Am J Perinatol, 2012;29(8):635-42.
doi:10.1055/s-0032-1311979
ACKNOWLEDGEMENT
We thank Dr. Josefina Romaguera for her assistance. We also recognize the job from the
staff at VITA Healthcare: Maribel Aviles, Patricia Rosa and Dr. Lauren Lynch, their medical
director.
The study limitation includes: small size of the
sample, short observational period, incomplete
charts, no availability of electronic medical record and a percent of patients lost to follow up.
Additional research is needed to identify other
benefits, population related differences and
compare results to a control group.
Despite 17α-hydroxyprogesterone availability,
its use is still not widely employed by all providers and many patients are unaware of its
accessibility. Education should be a key to increase patients and providers compliance with
ACOG recommendations. Continuation of this
study will provide more information regarding
patient selection, more accurate pregnancy
and neonatal outcome results. It will also help
identify other risk factors in establishing other
criteria for better treatment and preterm birth
prevention.
REFERENCES
1. Prediction and prevention of preterm birth. Practice Bulletin
No. 130. American College of Obstetricians and Gynecologists.,
Obstet Gynecol 2012;120:964-73
2. March of Dimes. Preterm Birth Statistics;2012. Available at:
28
RESUMEN
Objetivo: Describir los resultados del embarazo y del recién nacido después de
recibir 17 α-hydroxiprogesterona para
prevención de parto prematuro en nuestra institución. Métodos: Cuarenta y dos
pacientes recibieron tratamiento por la
compañía ‘VITA Healthcare’. La información se obtuvo de los expedientes
médicos. Resultados: Se observó un aumento en la edad gestacional promedio
al momento del parto. De igual forma se
identificó una ganancia en las semanas de
gestación al momento del parto en comparación con el parto prematuro anterior.
Discusión: Más del 75% de las pacientes
prolongaron su embarazo con el uso de 17
α-hydroxiprogesterona. Se debe continuar
el estudio para estratificar las pacientes
según factores de riesgo y establecer criterios para mejorar la prevención de partos prematuros en nuestra comunidad.
PROFILE OF PATIENTS ADMITTED WITH
INFECTED SKIN ULCERS AT BELLA VISTA
HOSPITAL MAYAGÜEZ
29
Brandie Astudillo MDa, Miguel Cruz MDa, Luis del Prado MDa, Renato Domenack MDa, Eva
Nasi MDa, Sergio Seche MDa, R. Iván Iriarte MDb*
Bella Vista Hospital Family Medicine Residency Program, Mayagüez, Puerto Rico.
Bella Vista Hospital Family Medicine Residency Program and Ponce School of Medicine and Health Sciences, Mayagüez & Ponce,
Puerto Rico.
*Corresponding author: R. Iván Iriarte MD - PO Box 7004, Ponce, Puerto Rico 00732. E-mail: [email protected]
a
b
ABSTRACT
The purpose of this study is to evaluate the characteristics of patients admitted to
Bella Vista Hospital in Mayagüez with a diagnosis of infected skin ulcer, the most
common microorganisms recovered in cultures, and their antimicrobial sensitivity
patterns. Methods: All patients discharged with the diagnosis of infected skin ulcer
from January 1 through December 31, 2012 were selected. Following variables were
extracted: sex, age, hospital stay, morbid conditions, antibiotics used, microorganisms identified on cultures and sensitivity of microorganisms to different antimicrobials. Prevalence rates were estimated for different conditions and different microorganisms. The use of empirical antibiotics were described and compared with the
antimicrobial sensitivity of the microorganisms. Results: The study population consisted of 98 subjects (54% female, 46% male). Mean age was 71 years old, with 71% of
subjects older than 65 years old. Prevalence rates of diabetes mellitus, peripheral vascular disease, hypertension and osteomyelitis were 74.5%, 74.5%, 79.6%, and 17.5%
respectively. The antibiotic most frequently used was piperacyllin-tazobactam (PTZ).
The organisms most frequently found on cultures were Staphylococcus (37.8%), distributed as 20.4% methicillin resistant and 17.3 sensitive to methicillin, followed by E.
coli (30.6%), Streptococcus (29.6%), and Pseudomonas (27.6%). The majority of microorganisms were sensitive to PTZ. There was a higher prevalence of osteomyelitis
in diabetic patients than in non-diabetic patients but the difference was not statistically significant. Conclusions: Antibiotic sensitivity patterns were consistent with the
expected, according to the literature. Empirically used antibiotics were appropriate
according to sensitivity patterns shown in the study.
Index words: profile, patients, infected, skin, ulcer, Bella Vista, Mayagüez
INTRODUCTION
Infected skin ulcers are one of the most common types of infection encountered by doctors in medical practice. Some authors report
that they could be responsible for 1-2% of
admissions to hospitals (1). They represent
an inflammatory microbial invasion of the epidermis, dermis and subcutaneous tissues,
frequently showing the classical signs of inflammation described by anciently as heat,
redness, swelling and pain, in addition to discharge. The skin is the largest organ of the
body and it is the most important barrier from
invasion by external injury. It prevents chemical, physical and biological agents to damage
or invade our organism, and also provides an
adequate mechanism of repair. When any external agents penetrate the barrier of the skin,
they may injure the underlying soft tissue, fat
layers, fascia and muscle.
The skin is typically colonized by an indigenous
microbial flora, which consists of a variety of
species of staphylococci, corynebacteria, micrococci, gram-negative bacteria and yeasts
(2). This flora may vary from a few hundred organisms in some areas to many thousand per
square centimeter in moist zones of the body
such as the groin and axillae. The organisms
in the normal flora may act as competitive inhibitors of pathogenic microbes. Breaks in the
skin, such as leg ulcers, burns and surgical
or traumatic wounds allow colonization with
a broader range of bacteria. Bacteria in skin
ulcers usually act along a spectrum that goes
from contamination, to colonization without
infection, and finally to infection. Colonization
is not necessarily associated with overt signs
of inflammation but can result in failure of the
ulcer to heal, poor granulation and increased
friability (3).
Direct infection of the skin occurs by invasion
of the epidermis, usually after damage to the
skin. Microbial disease of the skin may also
occur by hematogenous spread of bacteria
or viruses like in the case of meningococcal
rash and measles, or by toxin-mediated damage from an infection or minor local trauma
elsewhere in the body, like in staphylococcal
scalded skin syndrome or streptococcal scarlet
fever.
Factors that contribute to the development of
infected skin ulcers include intrinsic characteristics of the patient such as: advanced age,
malnutrition, dehydration, impaired mobility or
sensation, decreased level of consciousness,
use of steroids, and presence of chronic conditions such as diabetes, especially if uncontrolled, smoking, peripheral vascular disease
or hypertension (1, 4). In a recently reported
case-series of patients with intractable leg ulcers, the authors reported that 58 out of 79 lesions (73%) had evidence of ischemic disease
(5). Other factors that contribute to the development of infected skin ulcers are external
mechanical in nature such as pressure, friction
and moisture.
When infection occurs, it usually requires treatment with antibiotics, including topical, oral or
parenteral. The decision concerning the route
of administration of antimicrobial agents, duration, and the need for hospitalization should be
based on the most likely infecting organisms,
the severity of the infection, and the presence
of ischemic disease or other aggravating factors. In addition to antibiotic treatment, other
interventions are necessary for the appropriate
management of infected skin ulcers, including
mechanical wound care and off-loading of the
limb. In some cases revascularization surgery
may be necessary (3, 6). More novel treatment
modalities that have been investigated with
success include hyperbaric oxygen and phototherapy with laser and ultraviolet C-light (7, 8).
The importance of prevention and early, aggressive treatment of infected ulcers cannot be
overemphasized. The previously mentioned
contributing factors are associated to the severity of these lesions, and severity is directly
associated to the risk of eventual limb amputation. Investigators at the University of Texas
Health Care Center in San Antonio established
a classification system of skin wounds in 360
diabetic patients using criteria of wound depth,
infection and ischemia. They found that the
outcomes were worse with increasing grade
of wound severity. Patients with infection and
30
31
ischemia were nearly 90-times more likely to
receive an amputation than patients with less
severe wounds (9).
The purpose of this study is to describe the
characteristics of patients admitted to Bella
Vista Hospital in Mayagüez with a diagnosis of infected skin ulcer, including co-morbid
conditions, the most common microorganisms
recovered in cultures, and their antimicrobial
sensitivity patterns.
METHOD
This was a cross-sectional study. The investigators obtained Internal Review Board approval from the Ponce School of Medicine and
Health Sciences (IRB # - 130205-LV). All of the
patients discharged from Bella Vista Hospital
in Mayagüez with the diagnosis of infected
skin ulcer from January 1 through December
31, 2012 were selected. The total study population consisted of 98 cases. The investigators reviewed each one of the medical records
extracting the following variables: sex; age;
admission and discharge dates: presence of
co-morbid conditions (Yes or No) including
diabetes mellitus, peripheral vascular disease
and arterial hypertension; antibiotics used on
admission; microorganisms identified on skin
ulcer cultures; and sensitivity of microorganisms to different antimicrobials.
The investigators extracted data from the hos-
32
pital records and imported them to Epi-info7®
software. Data analysis included frequency distributions of categorical variables, and means
and standard deviations for numerical- continuous variables. Prevalence rates were estimated for co-morbid conditions such as diabetes mellitus and peripheral vascular disease.
The prevalence rate of osteomyelitis was estimated and compared between diabetic and
non-diabetic patients. The prevalence rates of
different microorganisms were also estimated.
The use of empirical antibiotics was described
and compared with the antimicrobial sensitivity
of the microorganisms.
RESULTS
The study population consisted of 98 subjects.
The sex distribution was 54% female (95% CI:
44, 64) and 46% male (95% CI: 36, 56). Mean
age was 71 years old, with 71% of subjects
older than 65 years old. Figure 1 presents
the distribution of the study population by age
groups.
The prevalence rates of diabetes mellitus,
peripheral vascular disease and arterial hy-
pertension were 74.5%, 74.5% and 79.6% respectively. The prevalence rate of osteomyelitis was 17.5%. These results are summarized
in Table 1.
The mean length of stay in the hospital for the
study population was 13.1 days with a standard deviation of 7.5 days and a range of 1031 days. Figure 2 shows the distribution of the
study population in groups according to hospital stay.
Table 2 shows the frequency of empirical use
for different antibiotics. Table 3 shows the
prevalence rate of different microorganisms
that grew in cultures.
The antibiotic most frequently used was piperacillin-tazobactam (PTZ), used in 65.3% of
subjects. The organisms most frequently found
on cultures were Staphylococcus (37.8%),
followed by E. coli (30.6%), Streptococcus
(29.6%), and Pseudomonas (27.6%). Figure
3 shows the distribution of subjects according
to the number of organisms cultured from the
lesions.
33
It can be observed that the most frequent occurrence was to have an ulcer infected with
only one organism, but 48% of the subjects
(47/98) had ulcers infected with two or more
organisms.
Table 4 shows the patterns of sensitivity of
different microorganisms to antibiotics. The
majority of microorganisms (70.0% of E. coli,
86.2% of Streptococcus, 66.7% of Pseudomonas) were sensitive to PTZ. As expected,
the majority of MRSA (95%) were sensitive to
vancomycin. The majority of organisms were
resistant to ciprofloxacin.
Table 5 shows the prevalence rate of osteomyelitis in individuals according to the presence
of different conditions.
There was a higher prevalence of osteomyelitis in diabetic patients (19.2%) than in non-diabetic patients (12.5%) but the difference was
not statistically significant (OR= 1.7; 95% CI:
0.46, 7.8).
DISCUSSION
This cross-sectional case study attempted to
describe a profile of patients admitted with infected skin ulcers in a community hospital. As
expected, the patients were primarily of an advanced age, with a mean age of 71 years and
71% of cases being 65 years or older. There
was a slight predominance of females in the
study population (54%) but the difference was
not significant, since the 95% Confidence Interval for the percentage of both sexes included the value of 50%.
Also as expected, the majority of cases also
had diabetes mellitus, arterial hypertension or
peripheral vascular disease, or a combination
of two or more of them. Although the study did
not include a control group for comparison, the
prevalence rates of these conditions appear to
be higher than expected in the general population of individuals of the same age.
Almost half of the subjects had infection with
two or more microorganisms. This is consistent with what can be found in other studies
reporting that most infected skin ulcers are
polymicrobial (10).
The most common microorganism seen was
Staphylococcus. This finding is also consistent with that reported by other authors who
have written about the subject. Most available
reports are consistent with the finding that the
most frequent agent isolated from infected ulcers is Staphylococcus aureus (3, 10, 11, 12).
In a systematic review of the literature Lima
et al. found that the most common pathogen
in infected diabetic wounds was Staphylococcus aureus, with a high percentage of methicillin resistant strains (MRSA) (11). In a caseseries with 195 patients with ulcers colonized
or infected with Staphylococcus aureus, the
authors report that 35 (18%) were methicillin
resistant (12). In another study, MRSA was recovered from 85 out of 137 (62%) cases with
abscesses or skin ulcers. The presence of
MRSA was significantly associated with obesity (13). In the present study, out of 37 lesions
where Staphylococcus species were isolated,
20 (54%) were methicillin resistant. E. coli,
Streptococcus species and Klebsiella were
also very frequent and almost equally prevalent.
Antibiotic sensitivity patterns were consistent
with the expected. The majority of microorganisms were sensitive to piperacillin-tazobactam
(PTZ) except MRSA’s that had a better sensitivity to vancomycin. The empirical use of
antibiotics appeared to be appropriate, since
the most commonly used antibiotic was PTZ.
In a randomized trial evaluating the efficacy of
different antimicrobial therapies for skin infections, the authors found that PTZ was equally
effective as moxifloxacin, a fluoroquinolone
(14). In the present study, results would suggest otherwise, since a much higher percentage of microorganisms were sensitive to PTZ
than to ciprofloxacin, another fluoroquinolone.
It is important to note that these antibiotic sensitivity results should not be generalized. Patterns of sensitivity may vary in different hospitals.
The study attempted to find a possible association between the presence of osteomyelitis
and diabetes mellitus or other conditions. Surprisingly, the prevalence rate of osteomyelitis
was only slightly higher in patients with diabetes mellitus (19.2%) than in patients without
diabetes mellitus (12.5%). The Odds Ratio of
1.7 was not statistically significant. There appeared to be a stronger association between
osteomyelitis and peripheral vascular disease,
with a prevalence rate of osteomyelitis equaling 20.8% in patients with peripheral vascular
disease and a prevalence rate of osteomyelitis equaling 8.0% in patients without peripheral vascular disease. The Odds Ratio of 3.0
however, was not statistically significant. In
this study, the overall prevalence rate of osteomyelitis was lower than for other authors
34
who have estimated this prevalence rate to be
about 50% in patients with infected foot lesions
(15).
French multicenter study. Diabetes Care. 2012 Mar; 35(3):61723.
13. Khawcharoenporn T, Tice AD, Grandinetti A, Chow D. Risk
factors for community-associated methicillin-resistant Staphylococcus aureus cellulitis--and the value of recognition. Hawaii
Med J. 2010 Oct; 69(10):232-6.
14. Gyssens IC, Dryden M, Kujath P, Nathwani D, Schaper N,
Hampel B, Reimnitz P, Alder J, Arvis P. A randomized trial of the
efficacy and safety of sequential intravenous/oral moxifloxacin
monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and
skin structure infections. J Antimicrob Chemother. 2011 Nov;
66(11):2632-42.
15. Richard JL, Lavigne JP, Got I, Hartemann A, Malgrange
D, Tsirtsikolou D, Baleydier A, Senneville E. Management of
patients hospitalized for diabetic foot infection: results of the
French OPIDIA study. Diabetes Metab. 2011 Jun; 37(3):208-15.
Since this is a cross-sectional study done only
in one hospital, there are limitations regarding
the ability to generalize the results. However,
there is no doubt that infected skin ulcers are
an important medical condition, responsible for
a fair percentage of hospitalized patients. In
this study the mean duration of hospital stay for
these patients was 7.5 days; more than three
quarters of the study population had hospital
stays longer than one week. This suggests that
the costs associated to hospitalizations with infected skin ulcers are high.
Further studies with larger samples and including multiple hospitals are needed to better identify risk factors for this condition and
other determinants of outcome during hospitalization. Knowledge from these studies will
be helpful to establish interventions aimed at
preventing and decreasing the impact of this
condition in our population.
REFERENCES
1. Currie CJ, Morgan CL, Peters JR. The epidemiology and cost
of inpatient care for peripheral vascular disease, infection, neuropathy, and ulceration in diabetes. Diabetes Care. 1998 Jan;
21(1):42-8.
2. Baron S. (Ed.) Medical Microbiology, 4th edition. University
of Texas Medical Branch at Galveston, Galveston, Texas. 1996.
3. Frank C, Bayoumi I, Westendorp C. Approach to infected skin
ulcers. Canadian Family Physician. 2005. 51:1352-1359
4. Musa HG, Ahmed ME. Associated risk factors and management of chronic diabetic foot ulcers exceeding 6 months' duration. Diabet Foot Ankle. 2012; 3
5. Ino K, Kiyokawa K, Akaiwa K, Ishida M, Furuyama T, Onohara
T. A team approach to the management of intractable leg ulcers.
Ann Vasc Dis. 2013; 6(1):39-45.
6. Mansilha A, Brandão D. Guidelines for treatment of patients
with diabetes and infected ulcers. J Cardiovasc Surg (Torino).
2013 Feb; 54(1 Suppl 1):193-200.
7. Bhutani S, Vishwanath G. Hyperbaric oxygen and wound
healing. Indian J Plast Surg. 2012 May; 45(2):316-24.
8. Chandrasekaran B, Chettri R, Agrawal N, Sathyamoorthy C.
Short-term multimodal phototherapy approach in a diabetic ulcer
patient. Singapore Med J. 2012 Jun; 53(6).
9. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care. 1998
May; 21(5):855-9.
10. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ,
Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer
AW, Pinzur MS, Senneville E, Infectious Diseases Society of
America. Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and
treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;
54(12):1679-84.
11. Lima AF, Costa LB, Silva JL, Maia MB, Ximenes EC. Interventions for wound healing among diabetic patients infected
with Staphylococcus aureus: a systematic review. Sao Paulo
Med J. 2011 May; 129(3):165-70.
12. Sotto A, Richard JL, Messad N, Molinari N, Jourdan N,
Schuldiner S, Sultan A, Carrière C, Canivet B, Landraud L, Lina
G, Lavigne JP; French Study Group on the Diabetic Foot. Distinguishing colonization from infection with Staphylococcus aureus
in diabetic foot ulcers with miniaturized oligonucleotide arrays: a
35
RESUMEN
El propósito de este estudio fue describir las características de pacientes admitidos al Hospital Bella
Vista en Mayagüez con diagnóstico de úlcera en la
piel infectada, incluyendo otras condiciones médicas, microorganismos más frecuentemente recobrados en cultivos y sus patrones de sensibilidad a
antibióticos. Método: Todos los pacientes dados de
alta con diagnóstico de úlcera en la piel infectada,
desde el 1ro de enero al 31 de diciembre de, 2012
fueron seleccionados. Las siguientes variables
fueron estudiadas: sexo, edad, estadia hospitalaria,
co-morbilidad, antibióticos utilizados, microorganismos identificados en cultivos y sensibilidad de los
microorganismos a diferentes antibióticos. Se estimaron tasas de prevalencia de diferentes condiciones y las tasas de prevalencia de diferentes
microorganismos. El uso empírico de antibióticos
se describió y se comparó con los patrones de sensibilidad de los microorganismos. Resultados: La
población del estudio consistió de 98 sujetos (54%
femeninas, 46% masculinos). La edad promedio
fue 71 años, con 71% de los sujetos mayores de
65 años. Las tasas de prevalencia de diabetes mellitus, enfermedad vascular periférica, hipertensión
arterial y osteomielitis fueron 74.5%, 74.5%, 79.6%
y 17.5% respectivamente. El antibiótico más frecuentemente usado fue piperacilina-tazobactam
(PTZ). Los organismos más frecuentemente aislados en cultivos fueron Estafilococos (37.8%),
distribuidos como 20.4% resistentes a meticilina
(MRSA) y 17.3% sensibles a meticilina (MSSA); E.
coli (30.6%), Estreptococos (29.6%), y Pseudomonas (27.6%). La mayoría de los organismos fueron
sensibles a PTZ. Hubo una tasa de prevalencia
más alta de osteomielitis en sujetos con diabetes
(19.2%) que en sujetos sin diabetes (12.5%) pero
la diferencia no fue estadísticamente significativa.
Conclusion: Los patrones de sensibilidad a antibióticos fueron consistentes con lo esperado y de
acuerdo a lo reportado en la literatura. Antibióticos
usados de manera empírica fueron apropiados de
acuerdo a los patrones de sensibilidad encontrados
en el estudio.
36
INICIOS DE VALIDACION DE LA ESCALA PARA
MEDIR CALIDAD DE VIDA EN PACIENTES CON
CANCER: Versión de Puerto Rico (ECVCA-PR)
Janelly Muriel Sanoguet MSa, José
Rodríguez Gómez MDa*
Programa Doctoral Sicología Clínica ,Universidad Carlos Albizu, San Juan, Puerto Rico.
Autor correspondiente: Jose Rodriguez Gomez MD – P.O. Box
902 3711, Old San Juan Station, San Juan, Puerto Rico 009023711. E-mail: [email protected]
a
*
RESUMEN
El propósito de este estudio pionero es
crear y comenzar a validar una escala
para medir las actitudes en áreas que
pueden afectar la calidad de vida en
pacientes puertorriqueños con cáncer.
A tales fines se creó la Escala para Medir Calidad de Vida en Pacientes con
Cáncer: Versión de Puerto Rico (ECVCA-PR). La finalidad del proyecto fue
ofrecer a los profesionales de la salud
un instrumento que permita medir la
calidad de vida del paciente oncológico. La muestra consiste de 32 pacientes (9 hombres y 23 mujeres), entre las
edades de 30 a 83 años que son atendidos en el Hospital Oncológico Dr. Isaac
González Martínez en San Juan, Puerto
Rico. Las propiedades psicométricas
del instrumento indican un índice de
confiabilidad (alfa de Cronbach) de
0.927 quedando 164 reactivos. Este índice es considerado excelente a pesar
de haberse obtenido una muestra muy
limitada.
unas masas o tumores dañando el funcionamiento de los órganos en donde se encuentra2,3. Los factores de riesgo de esta enfermedad son múltiples y complejos, a los cuales
usualmente, nos encontramos expuestos
constantemente, entre ellos podemos mencionar: el uso de tabaco, la ingesta de alcohol
excesiva, las dietas altas en grasas saturadas
y con aditivos, la exposición solar sin protección, las radiaciones ionizantes en forma indiscriminada, los carcinógenos ocupacionales, la
contaminación atmosférica, algunos agentes
infecciosos, la actividad sexual sin protección
y la susceptibilidad genética4,5. Así como en
muchas partes del mundo, en Puerto Rico las
tasas de prevalencia de cáncer van en aumento aunque de manera paulatina6. El cáncer se
ha convertido en la segunda causa de muertes
luego de las enfermedades cardiovasculares6
siendo entre los más comunes: el de próstata
(46.2%), senos (34.3%), colon y recto (13.5%
en hombres y 14.5% en mujeres), útero (8.0%)
y el de pulmón (5.1% en hombres y 4.2% en
mujeres)7.
INTRODUCCION
El cáncer puede ser tratado con diferentes
acercamientos; quimioterapia, radioterapia, inmunoterapia y cirugía o combinaciones de estos. Dichos métodos tienen diferentes grados
de efectividad dependiendo de la estadía del
tumor, su agresividad y composición celular,
además de su propagación a tejidos adyacentes. Lamentablemente muchos de los tumores
no son detectados a tiempo lo cual limita el
proceso de cura de la enfermedad afectando
a su vez la calidad de vida del paciente. Se
ha comprobado que el estado fisiológico del
paciente está fuertemente relacionado a su
calidad de vida8,9. Tan temprano como en el
1949 se implementó la Escala de Incapacidad
de Karnofsky, que evaluaba el efecto de la
quimioterapia en los pacientes y en su funcionamiento diario10,11,12. Se entiende que fue la
primera escala desarrollada para medir la funcionalidad de los pacientes con enfermedades
crónicas según planteado por Velarde-Jurado
y Ávila-Figueroa12.
El cáncer es una de las enfermedades más
prevalentes en Puerto Rico y de las primeras
tres enfermedades que más matan a los puertorriqueños1. Se define la enfermedad, en
forma simple, como un crecimiento anormal
de células que se salen de control, formando
La calidad de vida según define la Organización Mundial de la Salud (OMS) es “un estado completo de bienestar físico, mental y social y no sólo la ausencia de enfermedad”13,14.
A pesar de esta definición, no hay una respuesta exacta a lo que corresponde “calidad de
Palabras indices: inicio, validacion,
escala, calidad, vida, paciente, cancer,
Puerto Rico
vida”. Para fines de múltiples estudios, lo que
muchos teóricos concuerdan es que la definición más completa del término, conlleva e
implica un sentido subjetivo y perceptivo del
paciente de lo que es salud de forma multidimensional y que cubre los aspectos físicos,
espirituales, sociales y psicológicos8,10-19.
En este estudio, pionero en Puerto Rico, se
desea comenzar a realizar la validación de
la Escala para Medir Calidad de Vida en Pacientes con Cáncer: Versión de Puerto Rico
(ECVCA-PR) en una muestra de pacientes
con diferentes tipos de cáncer del Hospital Oncológico Dr. Isaac González Martínez en San
Juan, Puerto Rico. Su finalidad es ofrecer a
los profesionales de la salud un instrumento
que permita evaluar con algún grado de objetividad la calidad de vida del paciente pre, peri
y post tratamiento oncológico y las actitudes
que este presenta. De este modo, habría más
certeza en cuanto a las necesidades del paciente y como se va sintiendo, por ejemplo,
a través de su tratamiento, lo cual puede ser
de utilidad para evaluar su sentir perceptivo y
subjetivo para con éste. La escala y sus reactivos fueron inicialmente creados por uno de
los autores (JRG), Gerontólogo, comenzando
por escuchar a pacientes de cáncer con diferentes tipos y estadías de cáncer, y lo que expresaban en diferentes áreas relacionadas a
su calidad de vida. De allí se comenzó a crear
reactivos para evaluarlos formalmente.
Los beneficios de conocer el nivel de calidad
de vida de un determinado paciente son: el
facilitar la toma de decisiones ante la selección de tratamientos adecuados para el/la paciente y cuales tienen efectos menos adversos
para él, ofrecer un mejor entendimiento del
estado emocional del/la paciente y reconocer
posibles estados psicológicos adversos que
puedan afectar su recuperación (i.e., depresión)20, y como comenzar a intervenir con ellos para beneficio del paciente. Font (1994)16
ofrece una contestación detallada sobre el por
qué estudiar la calidad de vida: “Conocer el
impacto de la enfermedad y/o el tratamiento a
un nivel relevante, diferente y complementario
al nivel biológico/fisiológico. Conocer mejor los
efectos secundarios de los tratamientos. Profundizar en el conocimiento del enfermo y su
adaptación a la enfermedad. Evaluar mejor las
terapias paliativas. Eliminar los resultados nulos de algunos ensayos clínicos, facilitando la
comparación de terapias alternativas. Facilitar
la rehabilitación de los pacientes”.
Al tratarse de un término que se construye de
37
manera subjetiva según la actitud del paciente, la mejor forma de poder medir la calidad
de vida es mediante el uso de instrumentos
válidos y confiables que sean culturalmente
sensitivos. Contreras-Martínez (2005)13 presenta tres tipos de cuestionarios para hacer
esto: los genéricos, los específicos para las
enfermedades y/o problemas de salud, y los
específicos en cuanto a síntomas. De igual
forma, estudiando la calidad de vida en pacientes oncológicos se utilizan mayormente las
siguientes cuatro pruebas:
1- EORTC QLQ-C30: Esta prueba se utiliza
para medir la calidad de vida en pacientes de
cáncer. Consta de 30 ítems e incorpora 5 escalas de funcionamiento, 3 escalas de síntomas, escala global del estado de salud/calidad
de vida y 6 ítems aleatorios19.
2- Rotterdam Symptom Check List (RSCL):
Esta prueba evalúa la calidad de vida en pacientes de cáncer. Es una prueba que consta de
39 ítems que se dividen en síntomas físicos,
síntomas psicológicos, actividades de la vida
diaria y calidad de vida global.
3- Cáncer Rehabilitation Evaluation System
(CARES): esta prueba se encarga de evaluar
la calidad de vida y las necesidades de rehabilitación en los pacientes de cáncer. Contiene
139 ítems pero contiene áreas bien específicas que algunos pacientes no pueden contestar. Se creó una versión más pequeña que
contiene 59 ítems. Se divide en seis partes:
una puntuación global de calidad de vida y 5
subescalas: física, psicosocial, interacción con
el médico, interacción con la pareja y sexual.
4- Functional Assessment of Cáncer Therapy
(FACT): Esta prueba, también, evalúa la calidad de vida en pacientes de cáncer. Contiene
28 ítems generales y 5 subescalas dependiendo del tipo de cáncer: mama, pulmón, colon,
cabeza y cuello e infección por VIH10.
El ECVCA-PR sería uno de los primeros instrumentos en Puerto Rico que permitiría la evaluación de calidad de vida en Puerto Rico desde
una perspectiva multidimensional y más integrativa en cuanto a los conceptos a tomarse
en consideración (i.e, aspectos fisiológicos,
psicológicos, espirituales y sociales). A pesar
de que se han hecho una variedad de estudios que toman en consideración el constructo
calidad de vida en el paciente con cáncer, son
pocos en los cuales se haya utilizado específicamente cuestionarios válidos, confiables
y adaptados a pacientes puertorriqueños. En
el Recinto de Ciencias Médicas, Facultad de
Enfermería de la Universidad de Puerto Rico,
en San Juan, se encuentra una de las pocas
investigaciones identificadas, la cual mide la
calidad de vida, muy particularmente, en pacientes de cáncer de mama que se encuentran
en tratamiento con quimioterapia. En dicha
investigación se utilizó como instrumento de
obtención de datos el FACT-B (Functional Assessment of Cáncer Therapy–Breast Cancer)
haciéndose una traducción de dicho instrumento y adaptación a Puerto Rico21. En esta
versión del FACT se miden seis áreas: “bienestar físico (7 premisas), social (7 premisas),
emocional (6 premisas), funcional (7 premisas), y otras preocupaciones (10 premisas)”
reportándose resultados satisfactorios en cuanto a una alta calidad de vida21. En este estudio se realizaron pruebas de confiabilidad,
dado a que la prueba fue traducida y adaptada
al español obteniéndose un nivel alfa de .902
considerado un nivel excelente de confiabilidad según Kline (2000)22.
Así como los estudios de calidad de vida están
tomando auge, también el cáncer está afectando cada día a más personas por la cantidad
de factores estresantes que nos rodean a nivel
ambiental y social y que influyen tanto en su
prevalencia como incidencia. Altos niveles de
estrés, por ejemplo, pueden tender a aumentar la producción de células cancerígenas y
disminuye las células del sistema inmunológico que defienden al cuerpo de las mismas23.
El nivel de mortalidad para estadías avanzadas de tumores agresivos tiende a ser alto y
lamentablemente, aunque los esfuerzos continúan en investigación oncológica, el manejo
y control de dichos tumores agresivos no ha
sido del todo exitoso24. Con el instrumento
ECVCA-PR se pretende evaluar las actitudes
de ese particular paciente oncológico en términos de áreas que afecten su calidad de vida.
Consideramos que la ECVCA-PR puede ser
un instrumento de utilidad para ser utilizado
por los clínicos en el manejo del paciente con
cáncer en PR.
METODO
Participantes
La muestra fue seleccionada por disponibilidad y estuvo compuesta por 32 pacientes,
entre las edades de 30 a 83 años que actualmente recibían tratamiento en el Hospital
Oncológico Dr. Isaac González Martínez, en
San Juan, Puerto Rico. La muestra incluyó 23
mujeres (72%) y 9 hombres (28%). A su vez, 6
de ellos se encuentran entre las edades de 30
a 50 años (19%), 21 se encuentran entre las
edades de 51 a 70 años (66%) y 5 son mayores de 71 años (15%), con un promedio de
59.5 años.
Diseño
El diseño de investigación es uno de carácter
expost facto, de carácter descriptivo. De igual
forma pretende comenzar a validar un instrumento que sea útil para Puerto Rico. Hernandez et al, (2006) plantean que los estudios descriptivos miden o recogen información de las
variables a estudiarse y son adecuados para
mostrar los ángulos iniciales de un fenómeno21. Por otro lado, la validación de instrumentos es un proceso arduo y sistemático en el
cual se requiere aplicar técnicas estadísticas
sofisticas de forma tal que se calculen índices
complejos (i.e, Alfa de Cronbach, rbis, valores
Eigen, entre otros) con los cuales se establezcan la utilidad de instrumento evaluado.
Consentimiento
Posterior a la aprobación por parte del Comité
de Investigación (IRB) del Hospital Oncológico
Dr. Isaac González Martínez, del protocolo de
administración y los debidos procedimientos
requeridos por el IRB, se contactó a la Administración del Hospital para informarle sobre la
investigación. Se realizaron múltiples visitas
al hospital en los cuales se lograba el reclutamiento mediante acercamientos directos a
los pacientes durante la toma de vitales, esperas para citas médicas y tratamientos de
quimio y/o radioterapia. Se le proveía con una
breve orientación de la investigación y se les
preguntaba si deseaban participar. De aceptar
participar se les orientaba sobre los consentimientos y sobre la confidencialidad del estudio. De encontrarse recibiendo tratamiento de
quimioterapia y/o radioterapia se le ofrecía el
cuestionario en el escenario de manera discreta, guardando la confidencialidad en todo
momento, con el consentimiento del participante, y sin revelar/mencionar su nombre para
proteger su identidad por cuestiones de seguridad y bienestar del paciente. Ninguna persona, excepto los investigadores, tuvo acceso
a la información provista por los participantes
del estudio. Los cuestionarios se mantendrán
guardados, de manera confidencial y serán
destruidos al pasar cinco años del estudio.
Este estudio no conllevó ningún riesgo conocido y servirá de beneficio para el desarrollo
de pruebas culturalmente sensitivas a la población puertorriqueña.
38
Instrumento
Hoja de datos socio demográficos. Se solicitó información que permitió describir las características de la muestra. Los datos que se
solicitaron fueron socio-demográficos usuales
tales como: género, edad, estado civil, último
grado obtenido, especialización del grado, universidad o instituto del cual obtuvo el grado,
ocupación, tipo de cáncer, etapa de la enfermedad y razón de la visita al hospital.
Escala para Medir Calidad de Vida en Pacientes con Cáncer: Versión de Puerto Rico (ECVCA-PR). Fue construida en su versión inicial
por uno de los autores (JRG) con el propósito
de poder evaluar la calidad de vida en pacientes con cáncer y sus actitudes, en Puerto Rico,
aun cuando se espera que pueda ser adaptada y sea de utilidad en otros países, muy
particularmente de habla hispana. Los ítems
o reactivos de la ECVCA-PR fueron obtenidas
inicialmente de entrevistas de pacientes con
cáncer en diferentes estadías y diferentes localizaciones corporales. El instrumento consta
de una escala tipo Likert cuyas respuestas se
dividieron en cuatro categorías: (0) nunca, (1)
un poco, (2) bastante y (3) mucho. La escala
ECVCA-PR consta de cuatro sub escalas que
evalúan áreas actitudinales que tienden a afectar la calidad de vida de pacientes, como lo
son áreas de: 1- Espiritualidad 2- Apoyo social
3- Psicológica y 4- Fisiológica, para un total de
173 reactivos. De igual forma tiene la escala
una sub parte cualitativa en que se le pregunta al paciente su sentir con relación a sintomatología experimentada según su tipo de
cáncer. En este estudio solo se evalúa la parte
cuantitativa de la Escala, esto es, su formato
Likert. En el formato Likert se le otorgó una
mayor puntuación a aquellas premisas que
representan actitudes que permiten una mejor calidad de vida de forma tal que, a mayor
puntuación mayor calidad de vida, con la excepción de algunas premisas de determinadas
sub-escalas en las cuales se invierten su valor
al momento de analizarlas psicométricamente
(i.e., Reactivo 40, “Tengo que quedarme en
cama durante todo el día porque no tengo a
nadie con quien compartir”; Reactivo 44, “Me
siento malhumorado casi todo el tiempo”; esto
es, significan lo contrario, a mayor puntuación
menor calidad de vida.
Se sometió la Escala a un procedimiento de
Validez de Contenido (por medio de jueces)
y el Índice de Validez de Contenido (ICV) por
medio de la fórmula de Lawshe (1975)25 utilizando la Tabla de Schipper para determinar
cuáles reactivos debían permanecer y cuáles
debían ser eliminados acorde a los jueces
evaluadores. Esto incluyó la evaluación por
un panel de cinco jueces compuesto por 2
médicos del Puerto Rico Children’s Hospital
y tres PhD de la Universidad Carlos Albizu.
La primera versión del instrumento contó de
353 reactivos. Se evaluó el Índice de Validez
de Contenido de los reactivos que se denominaron como esenciales por los jueces, dando
una puntuación de 1.00, siendo una validez
sumamente alta y eficiente para poder componer la escala acorde con las sugerencias
de Kline (2000)22. Luego de hacer la exclusión
de reactivos acorde con la indicación de los
jueces quedaron 173 reactivos, con los cuales
se constituye la escala para ser administrada
y proceder a realizar los análisis psicométricos
(i.e., análisis de factores).
Procedimiento
Para llevar a cabo el estudio se logró mediante
acuerdos escritos con la administración del
Hospital Oncológico Dr. Isaac González Martínez en San Juan, Puerto Rico, y de su Comité
de Investigación Institucional (IRB) tener acceso a los predios del hospital y a los pacientes
dentro de las facilidades del mismo. Se tenía
acceso al hospital dos días a la semana desde
las 8:00 am hasta las 12:00 pm durante cuatro meses consecutivos. Durante ese tiempo
se realizaban convocatorias y orientaciones a
los pacientes disponibles, y, de estos estar de
acuerdo a participar, se les daba y explicaba la
hoja de consentimiento y se llenaba en forma
oral la hoja de datos socio-demográficos y el
ECVCA-PR. Al terminar cada cuestionario se
le agradecía la oportunidad de participar y se
guardaba en archivos apartes el cuestionario y
el consentimiento.
Análisis estadísticos
Se llevaron a cabo análisis estadísticos descriptivos de los resultados demográficos, al
igual que se evaluaron las propiedades psicométricas del instrumento. Entre estas se llevaron a cabo análisis de consistencia interna
(i.e., alfa de Cronbach) para conocer la confiabilidad del instrumento. También se realizaron análisis por cada subescala, incluyendo
en aquellos casos que permitía la cantidad
muestral realizar análisis por género. Se utilizó
el programa estadístico IBM SPSS Statistics
versión 18 para llevar a cabo los análisis. Se
estableció un nivel alfa de 0.05 para determinar significancia estadística de los resultados
obtenidos. Inicialmente se procedió a evaluar
39
la escala con 173 reactivos, posteriormente
se procede a evaluar la escala eliminando
aquellos reactivos inadecuados a partir de el
análisis de factores, con lo cual la escala final
consta de 164 reactivos.
RESULTADOS
Se describen a continuación los resultados
descriptivos además de los índices psicométricos de la escala general y sub escalas de
la ECVCA-PR. La prueba con 164 reactivos
obtuvo un índice alfa de Cronbach de 0.927
lo cual la caracteriza como de excelente confiabilidad22. A pesar de que la muestra es reducida, Kline (2000)22 argumenta que según aumente la muestra, usualmente aumentará a su
vez el alfa de Cronbach, atribuyéndole mayor
confiabilidad.
Luego de realizar las pruebas de confiabilidad del instrumento completo, se realizaron
pruebas de confiabilidad de cada una de las
sub-escalas por las cuales está dividido el instrumento: espiritualidad (16 reactivos), apoyo
social (42 reactivos), psicológica (56 reactivos)
y fisiológica (50 reactivos).
Al realizar las pruebas de confiabilidad de la
primera sub-escala (espiritualidad), se obtuvo
un alfa de Cronbach de 0.858 siendo una de
magnitud alta. Además cabe resaltar que fue
esta la escala que más aceptación cualitativa
recibió de los pacientes. La sub escala de
apoyo social puntuó con un alfa de Cronbach
de 0.868 lo cual demuestra un índice de confiabilidad alto. La sub-escala psicológica fue
la que mayor confiabilidad obtuvo puntuando
con un alfa de Cronbach de 0.917. La sub-escala de aspectos fisiológicos obtuvo una alfa
Cronbach de 0.732 siendo la sub-escala mas
débil aun cuando Kline (2000)22 sugiere que un
indice alfa Cronbach de .70 en adelante es adecuado (Véase Tabla 1)
DISCUSION
El cáncer es una enfermedad la cual, dado a
la cantidad de factores de riesgo que posee
y a las cuales hoy día muchos de nosotros
nos exponemos en exceso, es importante
continuar investigando. Siendo el cáncer una
de las primeras causas de muerte en Puerto
Rico, es esta una de las enfermedades en la
cual el paciente tiende a sufrir en diferentes
momentos desde el diagnostico hasta el tratamiento. Lo anterior trae consigo posibles efectos secundarios que afectan grandemente la
calidad de vida de esos pacientes. La Escala
para Medir Calidad de Vida en Pacientes con
Cáncer: Versión de Puerto Rico, permitirá que
se pueda evaluar las necesidades del paciente pre, peri y post tratamiento en términos
actitudinales, ayudando a los profesionales de
la salud en la toma de decisiones en cuanto a
qué es lo mejor para el paciente tomando en
consideración aspectos espirituales, fisiológicos, psicológicos y de apoyo social.
40
Durante la administración se obtuvo una
muestra de 32 pacientes de los cuales 23 eran
mujeres y 9 eran hombres todos recibiendo
tratamiento en el Hospital Oncológico Dr. Isaac
González Martínez. La muestra posee edades
desde los 30 a 83 años, una dispersión amplia
con un promedio de 59.5, características que
pudiesen afectar los resultados en términos de
experiencias de vida, madurez para afrontar
realidades y manejo de crisis.
mienda, de igual forma, se realice estudios
de carácter cualitativos considerando expresiones adicionales que el paciente haga durante la administración del mismo que poseen
mucho valor investigativo y humano. De igual
forma se procederá en futuros estudios a
evaluar la parte cualitativa del ECVCA-PR. En
términos generales la ECVCA-PR puede ser
utilizada para evaluar el constructo “Calidad
de vida” y los aspectos actitudinales en pacientes con cáncer en PR.
Las mujeres predominaron en la muestra, al
igual que fueron más accesibles a participar
del estudio. De hecho cualitativamente eran
las que mejor disposición tenían para participar en el estudio/s.
Agradecimientos
Aun cuando el instrumento tenía una duración
de 20 a 30 minutos la condición en que se encontrase el paciente al momento de administración pudo ser un factor que influyera los resultados dependiendo del estado del paciente
al momento de ser evaluado.
El alfa de Cronbach final puntuó .927, mostrando ser un instrumento con un excelente
índice de confiabilidad según Kline (2000)22.
Este valor a pesar de haberse conseguido
con una muestra reducida, señala la teoría
de Kline que al aumentar la muestra, usualmente aumenta también la confiabilidad del instrumento. Por lo tanto, la escala ECVCA-PR
muestra ser de utilidad para poder evaluar las
actitudes, tomando en consideración diferentes aspectos que influyen la calidad de vida de
los pacientes con diferentes tipos de cáncer
en Puerto Rico.
De todas las sub-escalas, el área fisiológica,
fue la única que obtuvo un alfa de Cronbach
bajo en comparación con las otras sub-escalas (alfa .732 con 50 reactivos). Se entiende
que a pesar de ser un valor adecuado, es bajo.
De hecho, los reactivos que la componen trabajan varias facetas importantes en la vida del
paciente como la sexualidad, nutrición, actividad física y sintomatología. Cabe resaltar que
la mayoría de la población al ser preguntada
sobre la sexualidad, se mostraron resistentes
y muchos no contestaban, explicando así una
de las causas por la cual la confiabilidad se
puedo haber visto afectada. También la falta
de muestra representó una limitación para el
estudio.
Es en esta dirección que se recomienda aumentar la muestra y poder realizar análisis
confirmatorios con el instrumento. Se reco-
Deseamos reconocer toda la ayuda provista
por todo el personal, muy particularmente de
enfermería, del Hospital Oncológico Dr. Isaac
González Martínez en San Juan, Puerto Rico
en la realización de este trabajo.
BIBLIOGRAFIA
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42
ABSTRACT
The aim of this pioneer study is to begin to create and validate a scale to
measure Quality of Life in cancer patients in Puerto Rico (ECVCA-PR) in
order to provide local health professionals with a reliable instrument that
help to measure attitudes that could
affect different patient’s quality of life
aspects and allows knowing the needs
of those cancer patients. Sample consisted of 32 patients (9 men, 23 women), between ages of 30 to 83 years
that were receiving services (i.e., hospitalization, treatment, and follow up)
at Dr. Isaac González Martínez Oncological Hospital in San Juan, Puerto
Rico. The psychometric properties of
the instrument indicate a reliability index (Cronbach’s Alpha) of 0.927 with
164 items, an excellent index according to the literature.
Case Reports/Reporte de Casos
EXACERBATION OF MOOD SYMPTOMS
ASSOCIATED TO PRIMARY AND SECONDARY
CARNITINE DEFICIENCY: A Case Report
ABSTRACT
Rarely screened in psychiatric patients,
primary and/or secondary Carnitine deficiency could be influencing and/or
mimicking the mood symptoms of our
patient population. The brain and specifically neurons are highly vulnerable
to impairments in oxidative metabolism, which can lead to neuronal cell
death and disorders of neurotransmitters causing changes in cognition and
behavior. For this reason, identification
of this disorder is important since its
treatment could result in symptom improvement and better quality of life of
our patients. We present a case where
exacerbation of mood symptoms was
associated to primary and secondary
Carnitine deficiency.
Index words: exacerbation, mood, symptoms, primary, secondary, carnitine, deficiency
INTRODUCTION
Carnitine is an amino acid derivative that plays a
vital role in energy production and fatty acid metabolism. It is mainly obtained through food, such
as meats and dairy products (1,2). It is manufactured by our body from two essential amino acids:
lysine and methionine. Carnitine facilitates the
transport of long-chain fatty acids across the mitochondria for beta-oxidation, and the removal of
potentially toxic free radicals and acylcoenzyme-A
metabolites from the inner aspect of mitochondrion as acylcarnitines (3).
Signs and symptoms of carnitine deficiency usually appear early in childhood as muscle weakness, vomiting, cardiomyopathy, low blood sugar,
and brain function abnormalities such as confusion and decreased cognitive functioning. Serious complications such as heart failure, hepatic
encephalopathy, coma and sudden death are a
risk (4).
Primary Carnitine deficiency results from an in-
43
Javier Santos-Cubiñá MDa*, Alexis TorresRodríguez MDa, Pedro A. Castaing-Lespier
MDa, Nuria Sabaté MDab, Ana Torres-Martin
MDa, Simón Carlo MDac
Psychiatry Residency, Ponce School of Medicine/VA Caribbean
Healthcare System, Ponce, Puerto Rico.
Child and Adolescent Psychiatry Fellowship, Ponce School of
Medicine/VA Caribbean Healthcare System, Ponce Puerto Rico.
c
Molecular Medicine Department, Hospital de La Concepción,
San Germán, Puerto Rico.
*Corresponding author: Javier Santos-Cubiñá MD - Box 7004
Ponce, PR 00732-7004. E-mail: [email protected]
a
b
born error of metabolism caused by deficiency
of the plasma membrane OCTN2 carnitine transporter, which prevents carnitine transport into the
mitochondrion. Secondary Carnitine deficiency is
associated to poor diet or malabsorption of carnitine, increased renal tubular loss of free carnitine (Fanconi Syndrome), dialysis, and/or drug
induced (4, 5).
Valproic acid has been related to secondary carnitine deficiency (2,6-15). One of the proposed
mechanisms is through inhibition of Alpha KetoGlutarate which is a coenzyme used in the synthesis of carnitine. Also, Valproic acid inhibits the
conversion of ammonia to urea through inhibition
of carbamyl-phosphate-synthase causing hyperammonemia, even in patients with normal liver
enzymes levels. Patients with elevated ammonia levels show continuous generalized slowing
of electroencephalography, alterations in level of
consciousness and decrease in neurocognitive
functions (5).
Case History
The patient is a 28-year-old Hispanic male with
history of Attention Deficit Disorder and Mood Disorder NOS. The patient was seen by the Psychiatry service in an outpatient clinic of the Ponce
School of Medicine/VA Psychiatry residency program post discharge from a one-week inpatient
Psychiatric treatment was instituted due to poor
impulse control, poor tolerance to stress, irritability and depressed mood. During the hospitalization the patient was prescribed Olanzapine 15mg,
Depakote 500mg four times a day, Lorazepam
0.5mg in the morning and was showing poor response.
The patient’s record was reviewed and it was
found that during the last hospitalization the patient had increased ammonia levels. After no clear
etiology was found (the patient’s liver enzymes
where within normal levels), the patient was referred to geneticist to evaluate a possible metabolic etiology. The genetic evaluation yielded that
the patient suffered from primary carnitine deficiency. Reevaluation of the patient’s medications
also yielded that Valproic acid could have exacerbated his carnitine deficiency. Also, it was found
that Valproic acid could be related to the increase
in ammonia levels. It was decided to discontinue
Valproic acid and begin supplement Levocarnitine 1980 mg daily. The patient was followed on
a weekly basis by the Psychiatry service. After
four weeks of treatment the hyperammonemia resolved, the carnitine deficiency was corrected and
the patient’s symptoms improved. The patient’s
pharmacotherapy was revised and he is currently
on daily doses of Citalopram 40mg, Olanzapine
10mg, Levocarnitine 1980 mg and a Vitamin/Antioxidant supplement. There have not been any
other Psychiatric hospitalizations after current
medication regime was established.
DISCUSSION
This case presents the opportunity to discuss exacerbation of irritability and mood symptoms in
a patient with an incidental discovery of hyperammonemia, which lead to further evaluation.
Genetic test resulted in the diagnosis of primary
Carnitine deficiency. Valproic acid has also been
known to cause secondary carnitine deficiency
and hyperammonemia, which could also have
contributed to the carnitine deficiency in this patient. Carnitine deficiency and hyperammonemia
are known to result in neurocognitive symptoms
exacerbation. Once carnitine supplementation began and Valproic acid was discontinued, carnitine
levels returned to normal, hyperammonemia resolved and the patient showed an improvement in
mood and irritability symptoms.
In 1996 The Pediatric Neurology Advisory Committee strongly recommended carnitine supplementation for children taking Valproic acid at risk
of developing a carnitine deficiency (14). This
raised the question if carnitine levels should be
monitored in patient’s receiving Valproic acid and/
or if carnitine deficiency should be screened in patients with neurocognitive symptoms.
Other pathologies that have also shown impairments in oxidative metabolisms are psychiatric
disorders such as anxiety, depression, Autistic
Spectrum Disorders (6, 13), Mental Retardation
(15), Cognitive Disorders, Dementias (1,12) and
Narcolepsy (10). Carnitine supplementation could
serve to ameliorate the biochemical abnormalities
found in these disorders and thus improve neurotransmitter levels, cognition and behavior.
44
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10. Miyagawa T, Miyadera H, Tanaka S, Kawashima M, Shimada M, Honda Y, Tokunaga K, Honda M. Sleep. 2011 Mar
1;34(3):349-53A.
11. Moreno, Macey, Schreiber: Carnitine levels in valproic acidtreated psychiatric patients: a cross-sectional study. J Clin Psychiatry. 2005 May;66(5)555-8.
12. Palacios HH, Yendluri, Parvathaneni, Shadlinski, Obrenovich, Leszek, Gokhman, Gasiorowski, Aliev: Mitochondrionspecific antioxidants as drug treatments for Alzheimer disease.
CNS Neurol Disord Drug Targets. 2011 Mar;10(2):149-62.
13. Palmeri L, Persico, AM: Mitochondiral dysfunction in autism
spectrum disorders: cause or effect?. Biochim Biophys Acta.
2010 Jun-Jul; 1797(6-7):1130-7.
14. Raskind, El-Chaar: The role of carnitine supplementation during valproic acid therapy. Ann Pharmacotherapy. 2000
May;34(5):630-8.
15. Rodriguez, de la Pena, Tutor, Paz, Fernandez, Rozas, Del
Rio: Carntine deficiency associated with anticonvulsant therapy.
Clin Chim Acta. 1989 15;181(2):175-81.
16. Sempere, Arias, Garcia-Villoria, et al: Study of inborn errors
of metabolism in urine from patients with unexplained mental
retardation. J Inherit Metab Dis. 2010 Feb;33(1):1-7.
RESUMEN
La deficiencia primaria y / o secundaria de
Carnitina podría influir, imitar o enmascarar
los síntomas de los pacientes psiquiátricos.
El cerebro y específicamente las neuronas,
son altamente vulnerables a las deficiencias del metabolismo oxidativo. Este tipo
de patología podría llevar a la muerte neuronal y a cambios en los niveles de neurotransmisores provocando cambios en la
cognición y el comportamiento. Por esta
razón, la identificación de la deficiencia de
carnitina primaria y/o secundaria es importante ya que su tratamiento podría resultar
en mejoría de los síntomas y una mejor
calidad de vida de nuestros pacientes. Presentamos un caso donde se exacerba el
estado de animo de un paciente siquiátrico
debido a deficiencia primaria y secundaria
de Carnitina.
RECTOVESTIBULAR FISTULA WITH NORMAL
ANUS: A treatment alternative
ABSTRACT
Congenital rectovestibular fistulas with
normal anus are a rare form of anorectal malformations, especially in the
Western hemisphere. Due to its rarity,
consensus on preoperative management, surgical technique and postoperative care is still in debate. We describe
a specific case with its management
plan and outcomes while providing an
up to date literature review on current
management trends.
Index words: rectovestibular, fistula,
normal, anus, treatment, alternative
INTRODUCTION
Anorectal malformations are well known congenital entities that comprise a spectrum of
anomalies. Rectovestibular fistulas with a normal anus, also known as H-type fistulas1-3,5,7-9 or
double termination of the alimentary tract2,3,5,9,
are an uncommon subtype comprising about
2.4 % to 3.2% of all anorectal malformations in
the Western Countries.1-3 Due to its rarity, consensus about preoperative management, surgical options and postoperative care have not
been established1,9. Several case series have
reported different approaches with variable results. We hereby present a case to evaluate a
specific management option and outcome.
Case History
A one-month-old-girl born at term was brought
to the Emergency Room by her mother who
noticed stool output from the vaginal vestibulum since two weeks. The mother denied fever, changes in behavior, constipation, vaginal
swelling, redness, tenderness, suppuration or
any other symptoms. On physical exam patient had a normally positioned anus with adequate sphincter tone. Stool output was evident
through the vaginal orifice. Pelvic sonogram
was performed which showed a normal pelvic
anatomy and skeletal survey films had no evidence of anomalies. A Barium enema failed to
45
Anwar Abdul-Hadi MDa*, Humberto LugoVicente MDb
Department of Surgery, UPR School of Medicine, Puerto Rico
Health Science Center, San Juan, Puerto Rico.
Department of Pediatric Surgery, UPR School of Medicine,
Puerto Rico Health Science Center, San Juan, Puerto Rico.
*Corresponding author: Anwar Abdul-Hadi MD - RR-36 PO Box
#8144 San Juan, Puerto Rico 00926. E–mail: anwar.abdul@upr.
edu
a
b
show a rectovestibular fistula. The patient was
taken to the operating room for a recto-genital
exam under anesthesia were a rectovestibular
fistulous tract one cm proximal to the dentate
line was easily canalized using a 24 GA angio
catheter (see Figure 1). The patient had a normal non-stenotic anus, without any associated
fissures, erythema, or evidence of infection or
trauma. The diagnosis was consistent with a
Congenital H-Type rectovestibular Fistula. The
child was discharged home.
Follow up in the Pediatric Surgery outpatient
clinics showed no clinical deterioration without
evidence of infection. Scheduling for surgery at
three months of age was done with a day before surgery admission for mechanical bowel
preparation with polyethylene glycol until clear
stool output, clear liquids diet and oral metronidazole preparation. At the operating room
under general anesthesia the child was placed
in a prone jackknife position. The perianal and
vaginal area were prepared and draped in sterile fashion. Silk 5-0 perianal sutures were used
for anal exposure and a small guide wire was
passed through the rectovestibular fistula for
anatomical demarcation. Silk 5-0 sutures were
placed at the rectal fistula opening to serve as
retraction during dissection (see Figure 2).
Needlepoint cautery was used for close circumferential dissection of the fistulous tract
in an anus-to-vestibular direction, dividing the
anterior external sphincter muscle in the midline. Dissection of the fistula continued up to
the vestibule (see Figure 3).
After resection of the fistula the sphincteric
muscles were approximated with interrupted
vicryl 6-0. A U-shaped anterior rectal flap was
created cephalad to the defect with a one cm
reported. Three weeks after discharge follow-up a small mucosal tag was observed along suture line. Patient was scheduled
for an exam under anesthesia a
week later, were the mucosal
tag was excised and approximated primarily with vycryl 6-0.
No evidence of re-fistulization
or anal stenosis was appreciated (see Figure 5). Pathology was pertinent for an acrochordon. During the next none
months the child has developed
properly, gaining weight with no
evidence of fistula recurrence.
DISCUSSION
wide apex and 3 cm proximal length bilaterally.
The flap was advanced over the previous fistula site and secured with interrupted vicryl 6-0
sutures to the anterior anal canal (see Figure
4). Pathology evaluation agreed with fistula
histology, no associated inflammatory changes
were reported.
The patient was transferred to ward with Acetaminophen for pain control, intravenous Piperacillin/Tazobactam, nil per os status and TPN
to maintain hydration and adequate nutrition.
The first bowel movement was achieved on
postoperative day #1. On day #3, with an intact suture line and no evidence of infection,
a clear electrolyte diet (PedialyteTM, Abbott
Laboratories) started. On day #4 the diet was
progressed to a half-strength milk solution. The
patient continued to stool with each feeding.
On postoperative day #5 diet was progressed
to regular formula, which was well tolerated.
The patient was discharged home on day #6
without complications and acetaminophen
elixir for pain control.
Follow up was done one week after discharge.
An intact suture line, no anal stenosis and no
evidence of infection were noted. No other
events of stool output through vestibule were
Due to its low incidence (0.7% - 3.2%) in
Western Countries1-4,6 among all the anorectal
malformations, H-type rectovestibular fistula
treatment lacks consensus1-3,5,6,8,9. Our case
debuted with passage of stool per vagina, the
most common presenting sign3-5,9, without evidence of infection or abscess formation by history and physical examination. Diagnosis was
difficult to achieved using conventional radiology (barium enema and pelvic sonogram) and
it necessitated an exam under anesthesia for
thorough examination and clear demarcation
of the fistulous tract. Multiple diagnostic workups have been suggested, including endoscopies4,5, contrast enemas and direct inspection
under anesthesia5. We agree on exam under
anesthesia being the best method for diagnosis4-6 with the added benefit of anatomical demarcation with a probe5,6, useful for operative
planning. Additionally, patients should be evaluated for any associated anomalies, especially
cardiac and pelvic (including presacral masses
and anal stenosis)3,4,6,7,9, as they may be present in up to 60% of patients3.
A procedure at a later age was planned as multiple reports suggest that it is not necessary to
manage this pathology emergently as long as
close follow up and adequate attention is provided by caretakers1,4,7. Multiple preoperative
regimens have been suggested for this type
of defect. We agree on bowel preparation as
it should theoretically reduce the risk of postoperative infection and wound dehiscence. We
opted for polyethylene glycol solution until evidence of clear stools, 24 hours of oral metronidazole and clear liquids diet. Other suggested
bowel preparations including three days con-
46
47
sisting of simple enemas twice daily, liquid
diet, and oral metronidazole1; saline enemas
and clear liquids diet for 24 hours2; saline enemas, liquid diet and oral metronidazole for 24
hours7; polyethylene glycol and cleansing enemas for 24 hours8; and liquid diet for one day
with saline enemas the night before the operation9. There is no evidence that suggests any
regime to be superior.
A transanal approach was done for resection
of fistula with an anterior endorectal mucosal
flap to cover the previous fistula site, similarly to the approach described by Park9 with
an added complete resection of the fistula instead of curettage. Complete resection of fistula with an anterior endorectal flap mobilization, as opposed to fistula curettage to cover
previous fistula site has been suggested as an
important measure to reduce the risk of recurrence4,6,8,9, and maintaining the posterior and
lateral aspects of the sphincters and perineal
body intact, thus preserving continence4,7,9.
We believe that the addition of fistula resection does not imply a more technically challenging surgery, while providing similar results
with preservation of the internal anal sphincters and the added benefit of complete fistula
removal; which theoretically should reduce
the recurrence rate. Other suggested surgical
approaches include anterior sagittal anorectoplasty5,6, posterior sagittal anorectoplasty,
fistulectomy, vestibuloanal pull-through, perineal repair6,7,9, fistulotomy and curettage with
or without a diverting colostomy, primary closure of the fistula with diverting colostomy5 and
endorectal advancement flap9. We also agree
that primary repair does not necessarily need
a protective colostomy, even in a patient with
a history of vulvar abscess or infection1-4,6,7
as long as the infection is well managed and
cleared, and good bowel preparation has been
achieved8.
The procedure was well tolerated and no evidence of recurrence was seen during hospitalization and follow up at two and 5 weeks
post operatively. At 5 weeks from the procedure a minor complication of a mucosal tag,
confirmed by pathology, along the right lateral
aspect of the suture line was noted which was
easily excised and repaired primarily in the
operating room. Continued follow up at none
months showed no signs of recurrence or infection, adequately healed wounds and good
sphincter tone. Postoperative intravenous antibiotics have been previously suggested7,9 and
we opted for postoperative broad spectrum antibiotics until discharge.
48
Histological evaluation does suggest a congenital etiology when an epithelialized tract
is evidenced without associated inflammatory
changes, as in our case1, 7. The anatomical
origin of the fistula one cm above the dentate line coupled with no history or evidence
of vestibular abscess, as seen in our patient,
also supports a congenital etilogy8,9, especially
when not related to any inflammatory or infectious presentation5,7,9. In patients with associated abscesses or cellulitis, differing surgical
treatment to clear the infection may reduce the
chances of recurrence or complications. Fistula recurrence and wound disruption are common3,7, recurrence is reported between 5% to
30%4, and may be associated with preoperative infections1,2. Complications can be varied;
perineal body dehiscence4, recurrence, anal
stenosis, bowel incontinence3,4. In our case a
small mucosal tag along the lateral aspect of
the rectal flap developed one month from operation, which was excised and closed primarily without recurrence.
Close postoperative follow up should be performed to evaluate for recurrence and the possibility of anal stenosis, not developed in our
patient. YazIcl et al. suggest the inclusion of
rectal dilation program on follow up. 2 Follow
up is also necessary to assess for fecal incontinence at a later age, although due to the preservation of the anal sphincters and preservation of a near normal anatomy outcomes are
expected to be good3.
It is necessary to reach consensus for the
treatment of this specific type of anomalies to
reduce comorbidities, especially associated
with fistula recurrence and reoperations3.
CONCLUSIONS
H-type recto-vestibular fistulas are rare malformations among the ano rectal anomalies
spectrum. Multiple approaches have been
suggested with different recurrence rates and
associated comorbidities. We favor direct inspection under anesthesia for diagnosis and
a transanal approach with resection of fistula
and anterior rectal mobilization over previous
fistula site. We believe it reduces recurrence
rates and has minimal comorbidities.
REFERENCES
1. Banu, T., M. Hannan, M. Hoque, M. Aziz, and K. Lakhoo.
"Anovestibular Fistula with Normal Anus." Journal of Pediatric
Surgery 43.3 (2008): 526-29. Print.
2. Yazlcl, Mesut, Barlas Etensel, Harun Gursoy, and Sezen Ozklsaclk. "Congenital H-type Anovestibuler Fistula." World Journal of Gastroenterology 9.4 (2003): 881-82. Print
3. Rintala, R., L. Mildh, and H. Lindahl. "H-type Anorectal Malformations: Incidence and Clinical Characteristics." Journal of
Pediatric Surgery 31.4 (1996): 559-62. Print.
4. Lawal, Taiwo A., Kaveer Chatoorgoon, Andrea Bischoff, Alberto Peña, and Marc A. Levitt. "Management of H-type Rectovestibular and Rectovaginal Fistulas." Journal of Pediatric
Surgery 46 (2011): 1226-230. Print.
5. Kim, Seong Min, Youn Joon Park, Soo Min Ahn, Jung Tak
Oh, and Seok Joo Han. "Infantile Vulvar Abscess with a Normal Anus: A Suspicious Sign of Rectovestibular Fistula."Yonsei
Medical Journal 51.5 (2010): 717-21. Print.
6. Lawal, Taiwo A., Aiwanlehi Eighemhenrio, and Felix O. Kumolalo. "Modified Transanal Repair of Congenital H-type Rectovestibular Fistula: A Technique to Avoid Recurrence." African Journal of Paediatric Surgery 10.1 (2013): 38-40. African Journal of
Paediatric Surgery. Web.
7. Li, Le, Ting-chong Zhang, Chong-bin Zhou, Wen-bo Pang, Yajun Chen, and Jin-zhe Zhang. "Rectovestibular Fistula with Normal Anus: A Simple Resection or an Extensive Perineal Dissection?" Journal of Pediatric Surgery 45.3 (2010): 519-24. Print.
8. Tsugawa, C. "Surgical Repair of Rectovestibular Fistula with
Normal Anus*1." Journal of Pediatric Surgery 34.11 (1999):
1703-705. Print.
9. Park, Jinyoung. "Use of an Ednorectal Mucosal Advancement
Flap to Treat H-type Rectovestibular Fistula in Patients with Normal Anus." Journal of Pediatric Surgery48 (2013): 247-50. Print.
RESUMEN
Las fistulas congénitas rectovestibulares que tienen ano en posición normal
son un tipo de malformación anorectal
extremadamente rara, especialmente
en Occidente. Dado su rareza, existe
debate en el consenso de su manejo
preoperatorio, técnica quirúrgica y cuidado postoperatorio. Describimos un
caso especifico de fistula congénita
rectovestibular con ano normal con un
plan de manejo y resultados excelentes a luz de la literatura actual de esta
condición.
49
50
AN UNEXPECTED
SIDE-EFFECT OF A
COMMONLY USED DRUG
Francisco Fernández González MDa*,
Samayra Miranda MDa, Mónica Santiago
Casiano MDb, José Nieves MDc, Edgardo
Adorno MDc, Ricardo Fernández González
MDc
ABSTRACT
We report a case of a 68 year-old-female patient with clinical features of
drug-induced lupus erythematosus after five years of treatment with amiodarone. She presented generalized skin
rash, arthralgia on upper and lower extremities, associated with difficulty to
walk. Remarkable laboratory results revealed a positive antinuclear antibody
test and a skin rash biopsy showing a
superficial and deep perivascular infiltrate of lymphocytes, histiocytes, and
eosinophils. Once the etiology of the
patient’s symptoms was identified, the
culprit drug was removed and she had
a complete remission of all signs and
symptoms. Early diagnose should be
recognized for prompt intervention and
avoid further complications associated
with this rare side-effect.
Index words: unexpected, side, effect,
commonly, drug
INTRODUCTION
Drug-induced lupus erythematous is an autoimmune disorder, caused by the exposure to
certain drugs. It could arise months to years
after exposure to drugs prescribed to treat
various medical conditions such as antihypertensives, antibiotics, and anticonvulsants. In
most cases, the cessation of the drug usually
resolves within days to months in a patient
with no underlying immune system dysfunction. Amiodarone induced-lupus is a rare entity reported in the medical literature. Typical
drugs mentioned to be the cause of this rheumatologic manifestation includes hydralazine,
procainamide, quinidine, isoniazid, diltiazem,
and minocycline. Although drug induced lupus
could be provoked by several medications,
amiodarone is another agent that may be unnoticed by the physician.
From the Internal Medicine Department San Juan City Hospital,
San Juan Puerto Rico.
Hematology and Oncology Section, VA Caribbean Healthcare
System and San Juan City Hospital, San Juan, Puerto Rico.
c
Pulmonary Program at San Juan City Hospital, San Juan, Puerto Rico.
*Corresponding author: Francisco Fernández-González MD Internal Medicine Department, San Juan City Hospital CMMS
#79 P.O. BOX 70344 San Juan, Puerto Rico 00936-8344. Email:
[email protected]
a
b
Case History
We described a 68-year-old female with a past
medical history of hypothyroidism, dyslipidemia, arterial hypertension, and cardiac arrhythmia consisting of supraventricular tachycardia being treated on an outside institution
with Amiodarone 200 mg orally daily since five
years prior to our evaluation. She arrived at the
emergency room complaining of generalized
skin rash, joint aches on upper and lower extremities of three weeks evolution. Symptoms
usually persisted throughout the day and most
of the time with mild relief to Acetaminophen.
For the last few days she has not been able to
walk because of her discomfort on both knees.
She denied fever, chills, oral ulcers, Raynaud’s phenomenon, recent infections, weight
change, or similar episodes in the past.
Upon physical exam, she was oriented in
three spheres with stable vital signs. Examination disclosed a malar rash associated with a
generalized erythematous maculopapular skin
rash mostly involving the thorax, abdomen,
neck, upper and lower extremities (see Figure
1). No joint effusion or swellings were identified. However, she had limitation on the range
of movements on extremities and difficulty to
walk due to arthralgia.
Laboratories were remarkable for an Antinuclear Antibodies (ANA) showing high levels in
a speckled pattern (above 320); low complements including C3: 89 mg/dl (90-180 mg/dl),
C4: less than 3.1 mg/dl (10-40 mg/dl); IgG: 621
mg/dl (700-1,600 mg/dl); IgM: 156 mg/dl (40230 mg/dl); sedimentation rate: 10 mm/hour
(<30 mm/hour); C reactive protein: 3.6 mg/
dl (<5 mg/dl); anti Jo1: negative; antihistone
antibodies: 0.4 units (0-0.9 units); anti-double
strand DNA: negative; rheumatoid factor: <10
IU/ml (<14 IU/ml); anti-centromere B antibodies: <0.2 AI (0-0.9 AI) ; Anti Ro: 5 EU/ml (<16
condition and the patient was
discharged without complications.
DISCUSSION
Amiodarone is an iodine rich
medication that is widely used
to manage cardiac arrhythmias. Multiple common organ
toxicities have been identified.
Most of these include damage to the lungs, thyroid, liver,
eyes and nerves (1). The usual side effects are nausea and
vomiting, hepatitis, alveolitis,
pulmonary fibrosis, microdeposits in cornea, bluish skin,
photosensitivity,
epididymitis, gynecomastia, peripheral
neuropathy, bradycardia, QTprolongation and thyroid function abnormalities. One of the
most common toxicity involves
the thyroid gland (2). On the
other hand, amiodarone induced-lupus has been rarely
mentioned in the literature.
Drug-induced lupus is an autoimmune disorder, similar to
systemic lupus erythematosus, caused by the exposure
to certain drugs. It usually
EU/ml); Anti La: 1EU/ml (<16 EU/ml); Antistreptolysin O: negative; Aldolase: 7.1 U/L (07.6 U/L); cyclic citrullinated peptide antibody:
negative; anti-ribonucleoprotein antibody: negative; hepatitis profile: negative; Parvovirus
B19 IgG: negative; TSH: 2.9 IU/ml (0.4-4 IU/
ml). Complete blood count and the metabolic
panel were unremarkable. Electrocardiogram
showed sinus rhythm with no arrhythmias.
In order to have a better clinical picture, a skin
biopsy was performed revealing a superficial
and deep perivascular infiltrate of lymphocytes, histiocytes, and eosinophils (see Figure
2). In view of these findings, amiodarone was
discontinued due a suspected drug-induced
lupus. The patient was treated with intravenous steroid therapy of methylprednisolone
60 mg intravenously daily for 10 days with oral
steroid tapering after discharge. Days later,
her skin rash progressively disappeared along
with her joints complaints. Hospital course basically showed a complete resolution of her
presents months to years after using the drug,
with an estimated 15,000 to 30,000 cases reported every year. It is equally common on
both genders, but typically described more in
Caucasians and older people (3). Many medications can induce lupus, but persistently the
most mentioned in the literature has been hydralazine, procainamide, isoniazid, quinidine,
diltiazem, and minocycline (4). Although antihistone antibodies are present in more than
95 percent of the cases, it is representative for
those taking procainamide, hydralazine, chlorpromazine, and quinidine (5). Anti-histone antibody is not always positive in drug-induced
lupus as noted in our case.
In drug-induced lupus the serum complement
components are usually normal, antinuclear
antibodies (ANA) are positive but anti-dsDNA
antibodies and anti-Smith are negatives while
anti-histones antibodies can be detected in
few cases. Circulating immune complexes and
non-specific increase in erythrocyte sedimen-
51
tation rate (ESR) and white blood cell count,
with eosinophilia are common findings. The
pathogenesis is not completely certain and
multiple theories are believed including abnormalities in the oxidative drug metabolism (6).
Our patient was treated successfully with
methylprednisolone to accelerate the improvement of her symptoms. After reviewing the laboratories and skin biopsy it was concluded that
she developed an amiodarone-induced lupus
for several reasons: the clinical picture, ANA
test positive, skin biopsy findings, and most
important the fact that after cessation of the offending drug her symptoms resolved without
sequela.
The incidence of side effects of amiodarone
ranges from 40 to 93 % (7). Amiodarone as etiology of drug-induced lupus is uncommon with
the literature reporting only few cases. Only
one case was found in a report conducted by
Susano et al (8).
In conclusion, we believe that once a patient
has classic signs and symptoms suggestive of
lupus, in addition to pertinent labs, a careful
review of patient’s medications should be evaluated in order to avoid underestimated drugs
such as amiodarone that can induce such unexpected reaction. Early diagnose should be
recognized for prompt intervention and avoid
further complications associated with this rare
entity.
REFERENCES
1. Reiffel JA, Estes NA, Waldo AL, Prystowesky EN, DiBianco
R. A consensus report on antiarrhyhmic drug use. Clin Cardiol.
1994 Mar; 17(3): 103-16.
2. Martino E, Bartalena L, Bogazzi F, Lewis E. Braverman. The
effects of amiodarone on the thyroid. Endocrine Reviews. 2001
April; 22(2): 240-54.
3. Borchers AT, Keen CL, Gershwin ME. Drug-induced lupus.
Ann N Y Acad Sci. 2007 Jun; 1108:166-82.
4. Fritzler MJ. Drugs recently associated with lupus syndromes.
Lupus. 1994 Dec; 3(6):455-9.
5. Yung RL, Johnson KJ, Richardson BC. New Concepts in the
pathogenesis of drug-induced lupus. Lab Invest. 1995 Dec;
73(6):746-59.
6. Rubin RL. Drug-induced lupus. Toxicology. 2005 Apr 15;
209(2):135-47.
7. Reader EA, Podrid PJ, Lown. Side effects and complications of amiodarone therapy. Am Heart J. 1985 May; 109 (5 Pt
1):975–83.
8. Susano R, Caminal L, Ramos D, Díaz B. Amiodarone-induced
lupus. Ann Rheum Dis. 1999 Oct; 58(10):655-6.
Acknowledgment: To Dr. Ricardo Fernández
González, director of Pulmonary Fellowship
and my brother, for being a good fellow and for
his support on the education for residents and
fellows at San Juan City Hospital.
52
RESUMEN
El caso se trata de un paciente femenino de 68 años de edad con características de lupus eritematoso inducido por medicamentos después
de cinco años de tratamiento con
amiodarona. Ella se presentó con
erupción de piel generalizada, artralgia de extremidades superiores e inferiores, asociado a dificultad para
caminar. Resultados significativos de
estudios de laboratorios demostraron
positividad en la prueba de anticuerpos antinucleares y la biopsia de piel
con erupción reveló infiltrado perivascular profundo y superficial de linfocitos, histiocitos y eosinófilos. Una
vez que la etiología de los síntomas
del paciente fue identificada, la doga
causante se descontinuó y ella tuvo
una resolución completa de todos
los signos y síntomas. El diagnóstico temprano debe de ser reconocido
para una intervención rápida y evitar
complicaciones asociada a esa entidad rara.
MENSTRUAL PSYCHOSIS: Presenting symptom
of bipolar disorder not otherwise specified in a
13-years-old Hispanic female
Javier Santos-Cubiñá MDa*, Pedro A. Castaing-Lespier MDa, Nuria Sabaté MDab, Ana
Torres-Martin MDa, Virgen M. QuiñonesFernandini MDab
Ponce School of Medicine/VA Caribbean Healthcare System
Psychiatry Residency Program, Mayaguez Site at “Centro de
Salud Conductual del Oeste”, Ponce & Mayaguez, Puerto Rico.
b
Ponce School of Medicine/VA Caribbean Healthcare System
Child and Adolescent Psychiatry Fellowship, Ponce, Puerto
Rico.
*Corresponding author: Javier Santos Cubiña - P.O. Box 7004
Ponce, Puerto Rico, 00732-7004. E-mail: [email protected]
a
ABSTRACT
Exacerbation of symptoms in mood
disorders such as bipolar disorders,
major depressive disorders and premenstrual dysphoric disorders could be
influenced by the hormonal changes of
the menstrual cycles in female patients.
Menarche has been related to onset of
mood symptoms, which at times have
been described as menstrual psychoses and could represent an early presentation of Pediatric bipolar disorders.
Pediatric bipolar disorders appear to be
characterized by less clearly defined
mood episodes, shorter duration of
these episodes, and different hallmark
symptoms than in adults. This report
describes a pediatric patient who had
no previous psychiatric symptoms and
for whom menstrual psychosis was the
presenting symptom of bipolar disorder
not otherwise specified.
Index words: menstrual, psychosis, bipolar, Hispanic, female
53
nature of the symptoms.
The diagnosis of bipolar disorder in the pediatric
population has been a controversial issue. The
presentation of the disorder tends to be varied in
children and adolescents; it has been confused
with Attention deficit, disruptive behavior disorders or mood disorders such as Pre-menstrual
dysphoric disorder. This often leads to misdiagnosis and mistreatment of the disorder, leading to complications and a poorer prognosis. In
order to clarify the diagnosis an accurate report
of the history of presenting signs, symptoms and
evolution of illness by caretakers is fundamental.
Six key symptoms have been described for pediatric bipolar disorder (2):
1) Decreased need for sleep
2) Unstable self esteem and/or grandiosity
3) Hypersexuality
4) Elevated Mood
5) Pressured speech and racing thoughts
6) Goal directed activity
Also, as stated by Dr. Ellen Liebenluft of the National Institute of Mental Health (NIMH), “the key
to diagnosis of bipolar disorder is the episodic
nature of the illness.”
As a symptom, menstrual psychosis has the following characteristics: a) acute onset, against a
background of normality; b) brief duration, with
full recovery; c) psychotic features: confusion,
stupor and mutism, delusions, hallucinations, or
a manic syndrome; d) a circa-mensual (approximately monthly) periodicity, in rhythm with the
menstrual cycle (1).
This report describes a pediatric patient who had
no previous psychiatric symptoms and for whom
menstrual psychosis was the presenting symptom of bipolar disorder not otherwise specified.
INTRODUCTION
Case History
Bipolar disorder is a significant mood disorder
since its prevalence is around 2.4% of the population, which may even be higher since milder
forms of the disease are often missed. It is the
6th leading cause of disability in adults and is associated with substantial impairment, economic
distress, chronic and debilitating medical conditions with a 10 to 20 times increase in risk for suicide when compared to the general population
in the United States (2). Furthermore, it not only
affects the person who suffers it, but it affects the
family of the patient as well due to the disruptive
The patient is a 13-years-old-Hispanic female
who had no previous Psychiatric history. She
was born in Yauco, Puerto Rico, lives with mother, father and 11-years-old sister. Has an 8th
grade education but has been home schooled
since December 2012 due to the onset of mood
symptoms that correlated with menarche. She is
Evangelical. The patient was hospitalized at the
Pediatric Intensive Care Unite of San Lucas Hospital in Ponce with a diagnosis of altered mental status rule-out of encephalitis and was being
treated prophylactically with antibiotics. After the
medical work up returned negative, which included blood work, obstetric & gynecology evaluation, neuro-imaging, lumbar puncture, toxicology,
BHCG, rheumatologic tests, she was consulted
to the Child Psychiatry service for further evaluation of altered mental status, mood and behavior.
At the time of the evaluation, the patient presented with elated/dysphoric mood, psychotic
symptoms such as paranoia and command type
auditory hallucinations, sexual and religious preoccupations, increased thought speed, and difficulty concentrating. She also presented with
anorexia and insomnia without feeling tired. The
onset of symptoms was five days prior to hospitalization and her menses had started two
days prior to hospitalization. Physically, she also
complained of a dull lower abdominal pain that
began with onset of menses. She denied obsession, compulsions or phobias. The patient denied
death wishes, suicidal ideas or homicidal ideas.
As collaterals, the patient’s mother and father
were interviewed for developmental and onset of symptoms history. Patient was born to a
22-years-old mother and an 18-years-old father.
Pregnancy was unplanned, but desired and welcomed. This was her mother’s first pregnancy;
she had prenatal care and there were no complications during pregnancy. Delivery was at 39
weeks through vaginal route with no complications. The patient weighed 8.4 pounds and measured 21 inches. She was not breastfed since
mother was taking antibiotics for an episiotomy.
Mother states that patient suffered from constipation and reflux. Several changes in formulas
were required before they could find one that
was tolerated by the patient. Mother states that
the patient did not present any developmental or
motor delays. There were no significant illnesses
or surgeries during his childhood. She states that
the she did not have academic difficulties and
that she had excellent grades. Patient did not
have social or language difficulties. There was
no history of physical, psychological or sexual
abuse. She did not have hyperactivity/inattention
or oppositional behavior history.
The onset of menarche was at 12-years-old on
January 2012, regular, with menses that would
last 5-7 days. The mother describes that with
menarche mood symptoms and behavior changes appeared. She describes that the patient displayed decreased need for sleep, grandiosity,
elated mood, pressured speech, wearing excessive make up. She describes that these symptoms would appear a few days prior to onset of
menses, exacerbate during menstruation and
resolve after menstruation ended. The episodes
reoccurred on a monthly basis and the symptoms
would exacerbate with each menstrual cycle. She
eventually developed excessive sexual and religious preoccupations along with paranoid ideas.
The symptoms were so severe that the patient
would not attend school during menstruation
since they interfered with her social and academic functioning. The mother states that on December 2012 the decision to begin home schooling
was made in order to protect her from the comments of other students and teachers. During the
menstrual cycles of January and February 2013
the patient worsened and included psychotic
symptoms and perceptual disturbances.
In order to help with mood, psychotic symptoms
and decreased sleep, Quetiapine 25 mg at bedtime was recommended during hospitalization.
Patient showed good response to medication:
sleep, mood and psychotic symptoms improved.
Symptoms resolved with the completion of menses. Patient was discharged and followed by the
psychiatry and psychology service on an outpatient basis. Patient’s symptoms remained stable
until the next menstrual cycle in which the patient
began to display decreased sleep, grandiosity,
elated mood, pressured speech, wearing excessive make up a few days prior to menses. There
were no psychotic symptoms. It was decided to
increase Quetiapine to 50 mg at bedtime with
good response and improvement of symptoms.
Once again, symptoms fully resolved with the
end of menses. The patient continued to be followed on an outpatient weekly basis. Upon arrival of next menses the patient remained stable
and no fluctuations in mood, behavior, sleep or
psychotic symptoms were observed. The patient
has remained stable for the past six months on
Quetiapine 50 mg at bedtime. The patient has
not required another hospitalization after psychotropics were initiated. The patient’s parents
have decided to continue home schooling for the
remainder of the academic year.
DISCUSSION
This case presents an opportunity to discuss
the appearance of a complex mood disorder in
a pediatric patient triggered by menarche and
exacerbated by menses. Complete neurological,
medical, gynecological, and rheumathological
workup revealed no organic cause for her symptomatology. The patient does not have any illicit
drug/alcohol use. As per family reports, there is
no family history of mental illness or suicide.
The patient appears to have a normal development and had no history of psychopathology until
menarche. Literature describes several cases of
psychotic, mood, and/or anxiety disorders that
are associated with menses (3). Estrogen is believed to have a neuro-protective effect and its
54
sudden drop prior to menstruation has been considered as a possible trigger for bipolar disorder
(4,5,6,7). A recent study reports that females with
a specific genotype may be more vulnerable to
fluctuating estrogen levels, which may then act
as a triggering factor for bipolar disorder due to
changes in the estrogen receptor (8).
The literature reviewed describes cases of periodic psychosis during puberty on a monthly basis
and lasting for 1-2 weeks in girls and boys developing hallucination, confusion, or excitement.
These episodes were found to be more common
in girls and correlated with the onset of menses
(9). Another study reviewed showed that from
nine pediatric patients with similar symptoms,
three had achieved remission by adulthood,
three had developed brief depressive symptoms,
and 3 had progressed to develop bipolar disorders (10). The episodic nature and the quality of
the patient’s symptoms led us to consider a diagnosis of bipolar disorder not otherwise specified.
In terms of treatment the literature reviewed suggests varied approaches. They range from thyroid hormone, clomiphene, atypical antipsychotics, mood stabilizers, and anticonvulsants (2).
After evaluating risk vs. benefits, in our case we
opted for Quetiapine. The rationale was that the
medication gave us the advantage of having antipsychotic as well as mood stabilizing properties.
Also, Quetiapine is well known to cause somnolence as a side effect, an effect that we desired in
order to manage the patient’s insomnia. Another
attractive aspect is that Quetiapine is known to
have less weight gain than other atypical drugs
such as Risperidone. In this case, the patient
had an excellent response upon dosage optimization and patient has been able to be maintained in remission of psychotic symptomatology.
schedule as soon as possible.
This report is significant for the occurrence of
menstrual psychosis as the presenting symptom of pediatric bipolar disorder. Early detection
of the symptoms could prove valuable since it
could help clarify the diagnosis and bring about
early treatment, which could prevent a functional
decline and avoid a higher number of hospitalizations.
REFERENCES
1. Brockington IF: Menstrual psychosis: a bipolar link to the hypothalamus. Curr Psychiatry Rep. 2011 Jun:13(3):193-7.
2. Washburn J, West A, Heil J: Treatment of Pediatric Bipolar
Disorder: A Review. Minerva Psichiatr. 2011 March;52(1):21–35.
3. Proudfoot J, Whitton A, Parker G, Doran J, Manicavasagar
V, Delmas K: Triggers of mania and depression in young adults
with bipolar disorder. J Affect Disord. 2012 Dec 20;143(1-3):196202.
4. Clifford J, Rowland J: The potential role of estrogens in relapse of recurrent affective psychosis. JRSM Short Rep. 2011
Oct;2(10):82.
5. Deuchar N, Brockington I: Puerperal and menstrual psychoses: the proposal of a unitary etiological hypothesis. J Psychosom Obstet Gynaecol. 1998 Jun;19(2):104-10.
6. Mahé V, Dumaine A: Estrogen withdrawal associated psychoses. Acta Psychiatr Scand. 2001 Nov;104(5):323-31.
7. Meinhard N, Kessing, LV, Vinberg M: The role of estrogen in
bipolar disorder, a review. Nord J Psychiatry. 2013 Mar 19.
8. Graae L, Karlsson R, Paddock S: Significant association of
estrogen receptor binding site variation with bipolar disorder in
females. PLoS One. 2012;7(2):e32304.
9. Abe K, Ohta M: Periodic psychosis of puberty: a review on
near-monthly episodes. Psychopathology. 1992;25(4):218-28.
10. Abe K, Ohta M: Recurrent brief episodes with psychotic features in adolescence: periodic psychosis of puberty revisited.
Psychiatry Clin Neurosci. 1998 Dec;52 Suppl:S313-6.
CONCLUSION
This case demonstrated the varied presentation
that bipolar disorder has in pediatric patients.
The patient’s initial presentation made it difficult
to diagnose since several factors needed to be
clarified, including ruling out a medical, gynecological, rheumathological, neurological or toxicological causes.
The key to the diagnosis was the history provided by parents of onset of symptoms and their
periodic relation to menses. After 3 months of
the initial evaluation the patient has continued to
be stable on current dose of Quetiapine 50 mg
at bedtime. The patient also has continued therapy with the Psychology service. We have recommended a reevaluation of pharmacotherapy
at six months of treatment. We have also recommended integrating patient to her academic
55
RESUMEN
La exacerbación de síntomas de los
trastornos del estado de ánimo como
el trastorno bipolar, trastorno depresivo mayor y el trastorno disfórico premenstrual, podría ser influenciada por
los cambios hormonales de los ciclos
menstruales en pacientes femeninas.
La menarquia se ha relacionado con la
aparición de los síntomas del estado
de ánimo, que a veces se han descrito
como psicosis menstrual y podría representar una presentación temprana
de un trastorno bipolar pediátrico. Cuando comparamos el trastorno bipolar pediátrico con el de adultos, en los
niños parece estar caracterizado por
episodios de cambios estado de ánimo
menos definidos, menor duración de
estos episodios y diferentes síntomas
característicos que en adultos. Este informe describe una paciente pediátrica
sin historial psiquiátrico previos y para
la que psicosis menstrual fue el síntoma debut de un trastorno bipolar no
específico.
Review Article/Artículo de Reseña
56
ETHNICITY AND GENETICS ARE MORE
IMPORTANT THAN DIABETES MELLITUS AND
HYPERTENSION IN PRODUCING
CARDIOVASCULAR EVENTS IN PATIENTS WITH
THE METABOLIC SYNDROME:
Emphasis in the Puerto Rico Population
Pablo I. Altieri MDab*, José M. Marcial MDa,
Héctor Banchs MDab, Nelson Escobales
PhDb, María Crespo PhDb
Department of Medicine and Physiology, UPR School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico.
Cardiovascular Center of Puerto Rico and the Caribbean, San
Juan, Puerto Rico.
*Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: [email protected]
a
b
INTRODUCTION
The recognition of the metabolic syndrome as
a pathological entity is one of the most important advancements in the management of cardiovascular disease in the last two decades.
Increasing awareness and research of this
syndrome has led to a deeper understanding
of how different metabolic risk factors such
as insulin resistance and vascular pathologies such as coronary heart disease (CHD)
interact and aggravate one another. In an
age when approximately 50 million Americans
are estimated to be afflicted by the metabolic
syndrome, it is imperative to comprehend this
cluster of risk factors to its fullest extent for the
sake of the public health of the United States
and Puerto Rico.
The National Cholesterol Education Program’s
Adult Treatment Panel III (ATPIII) identified
six components of the metabolic syndrome
that relate to cardiovascular disease (CVD):
abdominal obesity, atherogenic dyslipidemia,
increased blood pressure, insulin resistance,
pro-inflammatory state and the pro-thrombic
state. Framingham data analysis demonstrated that the metabolic syndrome alone predicted approximately 25% of all the CVD of new
onset, but in the absence of diabetes, did not
raise the 10-year risk for CHD to above 20%,
which is the threshold for a CHD-risk equivalent according to the ATP. The metabolic syndrome without diabetes raises the 10-year risk
for CHD to in between 10 and 20%. Lately
Tillin and associates reported the relationship
between metabolic risk factors and incident
cardiovascular diseases in European, South
Asian and African Caribbean and reached the
ABSTRACT
Metabolic syndrome is a cluster of risk
factors for cardiovascular disease that
affects an estimated 50 million Americans. The present article reviews the
metabolic syndrome with respect to its
definition, epidemiology, pathophysiology and management. A primary focus
in research has been to elucidate the
processes determined to cause insulin
resistance, the fundamental mechanism
underlying the metabolic syndrome.
Namely, the incidence, component
characteristics and complications of
the metabolic syndrome in the island
of Puerto Rico are described alongside
the fact that the metabolic syndrome
may be milder in Puerto Rico than in
the mainland United States because
it is characterized by less aggressive
coronary disease and a relatively normal lipid profile. This suggests that the
cardiovascular complications are more
influenced by genetics and culture than
diabetes mellitus and hypertension.
Index words: ethnicity, genetics, diabetes, hypertension, metabolic, syndrome
conclusion that ethnic differences measured
metabolic risk factors did not explained differences in coronary heart disease incidence.
The apparently greater association between
diabetes and stroke risk in Asia African Caribbean compared with Europeans merits further
study. We want to comment their ideas with
our data where ethnicity is more important in
the development of heart and brain vascular
events than diabetes and hypertension (Jam
Col Cardiol 2013; 61 (17) 1777-1786).
The Components of the Syndrome
There has been controversy in the past few
years about the definition of the metabolic syndrome. Recently, the need for a global definition has brought about the initiative of the In-
ternational Diabetes Federation (IDF) and the
American Heart Association/National Heart,
Lung, and Blood Institute (AHA/NHLBI), joined
by the World Heart Federation, International
Atherosclerosis Society, and International Association for the Study of Obesity to develop
one unified definition of the metabolic syndrome. Furthermore, it has been agreed that
abdominal obesity should not be a prerequisite
for diagnosis but one of the 5 criteria.1 Three of
5 following risk factors establishes diagnosis:
1) Elevated waist circumference (cut points
based on population and country-specific definitions; it is recommended that the IDF cut
points, 94 cm or more in men and 80 cm or
more in women, be used for non-Europeans
and either the IDF or AHA/NHLBI cut points,
102 cm or more in men and 88 cm or more
in women, be used for people of European
origin until more data is available), 2) triglyceride count equal or greater than 150 mg/dL,
3) high density lipoprotein (HDL) level less
than 40 mg/dL in men and 50 mg/dl in women,
4) blood pressure equal or greater to 130/85
mmHg, and 5) fasting blood glucose equal or
greater than 100 mg/dL. Certain combinations
of metabolic syndrome components confer
greater risks of developing mortality and CVD.
A 10-year study evaluating the progression of
the metabolic syndrome and its components2
determined that participants who entered the
syndrome having a combination of abdominal
obesity, high blood pressure and hyperglycemia had a 2.36-fold increase in the incidence
of CVD and a 3-fold increase in mortality in
general. This study determined two risk factor
combinations that confer a greater risk of cardiovascular morbidity and mortality compared
with the others: 1) high blood pressure along
with either central obesity and hyperglycemia,
or 2) high blood pressure along with dyslipidemia.
Pathophysiology
Insulin Resistance
Insulin resistance is a fundamental mechanism underlying the metabolic syndrome and
its components. Insulin is an anabolic hormone that exerts its effects primarily by promoting glycogen synthesis in the liver and
muscle, increasing triglyceride synthesis in adipose tissue and augmenting protein synthesis
and inhibiting proteolysis. Therefore, the consequences of insulin resistance are multiplefold. Magnetic resonance spectroscopy studies have determined that insulin resistance
in skeletal muscle manifests specifically as a
reduction in insulin-stimulated glucose transport into the cell via the Glucose Transporter–4
(GLUT-4).3 This reduced insulin-stimulated
glucose transport is caused by lipid overload
in the form of accumulation of long-chain acylCoA (LCCoA) and diacylglycerol (DAG) inside
the skeletal muscle cell. The lipid overload
stimulates the serine/threonine kinase cascade and phosphorylation of critical insulin receptor sites (IRS-1), thus inhibiting IRS-1 binding and activation, leading to reduced glucose
transport and subsequent hyperglycemia.4 In
order to compensate for tissue’s resistance to
the metabolic effects of insulin, the pancreas
increases its secretion, resulting in systemic
hyperinsulinemia.
There have been a number of processes determined to cause this insulin resistance,
but they can be categorized into two general
mechanisms: lipid overload and inflammation/
cytokine-induced. The lipid overload inside
skeletal muscle, the liver and other tissues is
brought on by increased fatty acid uptake; increased synthesis within the tissue involved
and diminished fatty acid oxidation and disposal. Insulin resistance in adipocytes leads
to increased lipolysis with subsequent elevations in free fatty acids and accumulation in
the ectopic sites mentioned above. Increased
fatty acid concentrations are typical of most
insulin resistant states such as type-2 diabetes and obesity. Thiazolidinediones (TZDs),
which are peroxisome proliferator-activated
receptor-gamma (PPARγ) agonists, have been
shown to increase insulin sensitivity by lowering plasma free fatty acid levels and ectopic
accumulation. These insulin sensitizers have
also been shown to shift the distribution of fatty
acids away from abdominal and intramuscular
deposits and into subcutaneous fat.5 Abdominal obesity in particular has been shown to be
most associated with insulin resistance and
the metabolic syndrome. It has been observed
that general obesity is not universal in the metabolic syndrome and insulin resistance. In addition, many obese subjects do not have metabolic abnormalities.
Secondly, insulin resistance is associated with
a systemic chronic inflammatory response
characterized by altered cytokine production
and activation of inflammatory signalling pathways. Activation of signalling intermediates
may be directly involved in serine phosphorylation and inhibition of binding and activation
of IRS-1. In addition, inflammatory cell/cytokine infiltration of adipose tissue may alter adipocyte lipid metabolism. In mice, fat-derived
57
cytokines activate the nuclear factor-B signalling pathway in hepatocytes and generate
systemic insulin resistance most likely through
the generation and actions of pro-inflammatory cytokines including interleukin-6 (IL-6) and
tumor necrosis factor- alpha (TNF-α).6 TNF-α
expression, which has been associated to insulin resistance for more than a decade, is
increased in adipose tissue in obese rodents
and humans7, and infusion of TNF-α antibodies reduces insulin resistance in rodents but
not in humans.7,8 It has also been found that
obesity increases the macrophage content of
adipose tissue.9 Moreover, subcutaneous adipose depots express significantly more leptin
and less TNF-α than abdominal depots.10 Clinically, each of the components of the metabolic
syndrome has been associated with increased
levels of C-reactive protein (CRP), a non-specific sign of inflammation.11
Adipose tissue is a hormonally active tissue,
producing cytokines, such as TNF-α and IL-6
that influence other body tissues. Adiponectin
is one such adipocytokine that increases insulin sensitivity by stimulating fatty acid oxidation,
decreasing plasma triglycerides and improving
glucose metabolism. Serum levels of adiponectin are reduced in individuals with visceral
obesity and states of insulin resistance. On the
other hand, weight loss induces adiponectin
synthesis12, as do thiazolidinediones through
the activation of PPARγ. Furthermore, a reduced plasma level of adiponectin has been
associated to people with a history of cigarette
smoking13 as well as to hypertensive patients.14
The role of adiponectin has not been definitely
established, but may be a factor explaining the
association between insulin resistance, hypertension and CVD. Another adipocytokine,
leptin, has been shown to improve glucose
homeostasis in lipodystrophic mice and humans, but has failed to correct hyperglycemia
in patients with obesity, supporting the concept
leptin resistance and its association to insulin
resistance states.15
Renin-Angiotensin System (RAS)
Activation of the renin-angiotensin system
(RAS) occurs in many cardiovascular disorders. The inhibition of this system by angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB)
has been mainstay therapy to reduce the onset and/or progression of hypertension, left
ventricular dysfunction, diabetic renal disease
and atherosclerosis. It has been theorized that
increased levels of angiotensin II (AII) inhibit
pre-adipocyte differentiation into mature adipocytes, thus impairing fat cell’s ability to store
fat, which in turn shunts fatty acids into visceral organs and worsening insulin resistance.16
Moreover, Angiotensin II, which acts largely
through the AT1 receptor, present in various
tissues such as the heart, blood vessels, kidney and adipocytes, is a strong stimulus for
increased oxidative stress fundamental in exacerbating endothelial dysfunction, inflammation and plaque formation through additional
vessel macrophage and T-lymphocyte recruitment. ACE inhibitors and ARB not only promote
adipocyte differentiation, but they also have
peripheral vasodilator effects that lead to improved skeletal muscle perfusion and glucose
uptake, improving insulin sensitivity. Furthermore, it has been shown that long and short
term inhibition of RAS can reverse or halt the
progression of endothelial dysfunction through
increased nitric oxide (NO) bio-availability, reduced oxidative stress and anti-inflammatory
modulation of cell surface and circulating adhesion molecules.17
Insulin Resistance and Atherosclerosis
Insulin resistance, inflammation, and atherosclerosis seem to be linked via the metabolic
syndrome, but it still has not been completely
elucidated whether the nature of this association is due either to a common molecular pathology related to insulin receptor signalling
(IRS binding and activation) or vascular consequences of insulin resistance. There are
two potential mechanisms: the deregulated
production of inflammatory cytokines and the
elevated levels of systemic oxidative stress.18
Thus, obesity-derived pro-inflammatory cytokines (i.e. IL-6, TNF-α) and reactive oxygen
species can generate peripheral insulin resistance but also directly impact on the endothelium to cause endothelial dysfunction and
initiate the atherosclerotic cascade. The inflammatory nature of atherosclerosis has been
further substantiated by demonstrating a correlation between high sensitivity CRP (hsCRP)
levels and a greater risk of cardiovascular
events, confirming hsCRP to be a strong and
independent predictor of future myocardial infarction and ischemic stroke.19 Routine plasma
CRP level readings have been suggested as
strategies for monitoring statin therapy, which
has proven anti-inflammatory other than lipidlowering effects.20
The process of atherosclerosis is characterized
by increased pro-thrombotic milieu, disordered
lipid accumulation and endothelial dysfunc-
58
tion. In experimental models that mimic insulin
resistance, vasodilation is impaired partly because of insulin’s inability to stimulate the activity of NO synthase, the enzyme responsible
for NO synthesis. It is now established that
the vascular endothelium must be intact and
that NO plays a critical role in mediating the
hemodynamic actions of insulin. In addition,
insulin resistance and the metabolic syndrome
often accompany elevated levels of fibrinogen
and plasminogen activator inhibitor 1 (PAI-1),
the main inhibitor of the fibrinolytic system.21
The more severe the metabolic syndrome, the
higher the plasma level of PAI-1.22 Increased
PAI-1 levels may predispose patients to the
formation of atherosclerotic plaques prone to
rupture with a high lipid-to-vascular smooth
muscle cells ratio as a result of decreased cell
migration.23
Circadian Rhythm and the Metabolic Syndrome
There have been numerous studies that have
shed light upon the relationship between the
circadian rhythm and the body’s cardiovascular and metabolic health. Common disorders of circadian behavior and sleep, such
as night-shift work and jetlag, are associated
with increased hunger, decreased glucose
and lipid metabolism and changes in hormonal
processes involved in satiety.24 Short-duration
and poor-quality sleep have been shown to
predict the development of type 2 diabetes
and obesity after age, BMI and various other
confounding variables are considered and
taken into account.25 In addition, the induction
of hunger may be associated to a reduction in
circulating levels of leptin brought on by sleep
deprivation.26 Cardiovascular disease and hypertension are also related with sleep loss, as
the risk of a fatal heart attack increases 45% in
individuals who chronically sleep 5 hours per
night or less.27
Management
Diet and Exercise
Lifestyle approaches to treating and preventing
the metabolic syndrome greatly improve metabolic parameters by reducing body weight and
increasing the level of physical activity. Multiple
studies of obese patients with type-2 diabetes,
hypertension or hypercholesterolemia have
shown that weight improves the cardiovascular profile, including glycemic control, in both
diabetic and non-diabetic individuals. Furthermore, lifestyle changes comprising reduced
total/saturated fat intake and increased polyunsaturated fat/fiber intake have been shown
to significantly reduce multiple metabolic and
inflammatory parameters such as hsCRP, central obesity and triglyceride levels.28
The Mediterranean diet has received much attention in the last few years as an ideal diet to
follow for the metabolic and cardio-protective
benefits it may confer. The ATTICA epidemiological study showed that adherence to the
Mediterranean diet was associated with 20%
lower odds of having the metabolic syndrome,
irrespective of age, sex, physical activity, lipids and blood pressure levels.29 The diet is
low in saturated fat, high in monounsaturated
fat, mainly from olive oil, high in complex carbohydrates from legumes, and high in fiber,
mostly from vegetables and fruits. Moreover,
the Mediterranean diet has been associated
to improvements in the blood lipid profile, in
particular HDL cholesterol and oxidized LDL,
decreased risk of thrombosis, improvements
in endothelial function and insulin resistance,
and a decrease in body fat.
Physical activity is a cornerstone in weight balance. However, only part of the beneficial effect of physical activity on the metabolic and
cardiovascular profile is mediated through
body weight changes. Physical activity improves insulin sensitivity, increases HDL levels, and lowers blood pressure. The ATTICA
study, which also evaluated the association
between physical activity and the prevalence
of the metabolic syndrome, showed that even
light-to-moderate leisure time physical activity
(<7 kcal/min expended) was associated with a
considerable reduction in the prevalence of the
metabolic syndrome, while regular, intensive
exercise was associated with a much greater
decrease.29 The level of physical activity needed for a beneficial impact on coronary risk remains controversial. The Center for Disease
Control and Prevention and the American College of Sports Medicine recommend the accumulation of at least 30 minutes of moderateintensity physical activity (equivalent to brisk
walking at 3-4 mph), on most days of the week.
Pharmacotherapy
Although intensified therapeutic lifestyle modifications may prevent the onset and progression of the metabolic syndrome, some patients
may require drug therapy. Although each of the
components, such as glucose intolerance, hypertension, and dyslipidemia, is an appropriate
target for treatment, newer therapies may treat
59
the syndrome centrally and more effectively,
thus modifying parameters collectively. Although traditional approaches to the separate
risk factors have proven effective, increasing
attention is now being directed at the management of insulin resistance and obesity.
One of the main obstacles patients with the
metabolic syndrome face is achieving and sustaining weight loss, and many times pharmaceutical treatments are required. Recently published guidelines recommend that adjunctive
drug treatment for obesity should be considered in patients with a body mass index (BMI)
of equal or greater than 30 or a BMI of 27-29.9
with medically complicated obesity.30 Orlistat, a
gastrointestinal lipase inhibitor, sibutramine, a
centrally acting monoamine reuptake inhibitor,
and rimonabant, an endocannabinoid receptor
antagonist, are approved for long term treatment of obesity, but all anti-obesity drug trials
have been limited by their high attrition rates
and lack of long-term cardiovascular morbidity
and mortality data.
TZDs, of which the mechanism of action was
explained above, have been used increasingly
over the recent years for the management of
diabetes and have greatly broadened the understanding of the pathophysiology of insulin
resistance. These peroxisome proliferator activator receptor agonists act at a nuclear level to
improve glycemia, decrease insulin resistance,
and variably decrease plasma triglyceride levels and increase HDL cholesterol levels.31
Specifically, pioglitazone reduced triglycerides
and increased HDL levels to the same degree
of either statins or fibrates in a large observational study.32 Metformin, another anti-diabetic
drug, has also been shown to decrease insulin
resistance, decrease hepatic glucose production, triglycerides and cholesterol. 33
The ongoing search for new strategies to combat the metabolic syndrome has shed light on
new molecules that may prove to be effective
therapeutic targets in treating the syndrome;
stearoyl-coenzyme A desaturase 1 (SCD1)
has come to the vanguard of this search.34 By
catalyzing the conversion of long-chain saturated fatty acids (SFAs) to monounsaturated
fatty acids (MUFAs), SCD1 promotes multiple
aspects of the metabolic syndrome. However,
it was subsequently established that an antiinflammatory function exists for SCD1, as its
inhibition or deletion in mice accelerates atherosclerosis.35 SCD1 may indirectly suppress
inflammation by preventing SFA induced tolllike receptor 4 (TLR4) inflammatory signalling
and SFA enrichment of membranes.35 Fortunately, recent in vivo studies have established
that SCD1 inhibition-driven atherosclerosis
can be completely prevented by the omega-3
polyunsaturated fatty acids in dietary fishoils,36 thus providing a novel and synergistic
approach in treating the metabolic syndrome
and atherosclerosis.
Hispanics and the Metabolic Syndrome
Presently, 45.5 million Hispanics live in the
United States, comprising 15% of the total
population. The majority of Hispanics in the
U.S are of Mexican origin (64%); Puerto Ricans (9%), Cubans (3.4%) and Dominicans
(2.8%).37 Hispanics are nearly twice as likely
to have diabetes as age-matched whites. The
high prevalence of diabetes in this ethnic population has been attributed to higher rates of
obesity38, highly atherogenic diets and genetic
susceptibility.39 Moreover, a genetic linkage of
increased susceptibility to insulin resistance in
Hispanic populations has been reported.40
The Puerto Rican populations in the island, the
U.S., and elsewhere pose a significant public health problem that should be addressed
specifically because of the distinct metabolic
characteristics this ethnicity may possess.
In Puerto Rico, the prevalence of diabetes is
more than 12.7% while in the U.S it is 8.2%.
The death rate per 100,000 people related to
diabetes has increased form 10.6% to 66% in
the last 4 decades41 and heart disease continues to be the leading cause of death in the Caribbean island. A recent cross sectional study42
performed in the capital city of San Juan,
Puerto Rico showed that the age standardized
prevalence of the metabolic syndrome was
38.1%, slightly higher than the prevalence of
34% found in the general United States population at or above 20 years of age. In addition, this study demonstrated that the prevalence of the metabolic syndrome significantly
rose with age, from 12.8% among participants
aged 21–29 years to 58.2% for participants
aged 70–79 years. Elevated glucose (49.8%)
and abdominal obesity (49.0%) were the most
common components of the metabolic syndrome in sample studied, followed by elevated
blood pressure (46.1%), reduced high-density
lipoprotein cholesterol (46.0%), and elevated
triglycerides (31.3%). Noteworthy is the fact
that, of the study sample, 36.7% was overweight and 40.8% was obese, a higher prevalence than the self-reported estimates for the
US population of 39.4% overweight and 24.7%
obese provided in the 2006 Behavioral Risk
60
Factor Surveillance System (BRFSS) by the
Centers for Disease Control and Prevention
for the US population.43
The inner workings of the metabolic have yet
to be elucidated to their finest degree, thus it
remains difficult to evaluate how they differ between specific ethnic populations. Nevertheless, it remains a possibility that the processes
involved in the syndrome, such as insulin resistance and endothelial dysfunction, are not
working in the same measure between Hispanic and non- Hispanic populations. It has been a
recurring theme that the interactions between
poor nutritional status, physical inactivity, and
genetic predisposition might contribute to the
disparities in the prevalence and characteristics
of the metabolic syndrome and its components
between ethnicities and the subgroups within;
this subject has been studied to the extent that
even the diagnostic criteria for the metabolic
syndrome established by the AHA/NHLBI have
been challenged when adapted to a specific
Andean population.44 Moreover, researchers
have found that a single DNA variation in the
form of a guanine base pair on a gene already
linked to a higher risk of Coronary Heart Disease (CHD) in other races confers a fivefold
reduction in risk in African-Americans.45
Previous data have supported the fact that
increased serum cholesterol levels produce
less myocardial infarctions in Puerto Rico than
in the mainland,46 however the validity of this
data may not be as strong today as when published nearly three decades ago as recent epidemiologic data show that, although mortality
from coronary disease and stroke has been
steadily decreasing in the United States in the
past four decades, it had been increasing in
Puerto Rico.47 In the other hand, recent work
studying the medical records of 173 patients
with metabolic syndrome who received treatment in the Cardiovascular Center of Puerto
Rico and the Caribbean has shown a group
devoid of aggressive coronary artery disease
with a relatively normal lipid profile except
for mild elevation of serum triglycerides, supporting the notion that Puerto Ricans in the
island acquire a milder form of the metabolic
syndrome than populations in the mainland
including both Hispanics and Caucasians.
Furthermore, several investigators have described that the incidence of ventricular tachycardia, a complication caused by remodeling
and ischemia of the heart, is lower in Puerto
Rico than in the United States48, even when
adjusting for a higher prevalence of the metabolic syndrome in Puerto Rico. In addition, the
prevalence of coronary heart disease is lower
in Puerto Rico than in the United States. Nonetheless, the prevalence of CHD in Puerto Rico
is increasing, as it was 50% lower than in the
United States in the 1980’s and it is only 20%
lower today. (U.S. Government Statistics); this
is most likely due to external factors such as
the increasingly unhealthy Puerto Rican diet
and sedentary lifestyle of many of the island’s
inhabitants. As clearly seen in our Puertorrican
population coronary artery disease, strokes
and the metabolic syndrome is less aggressive than the U.S.A. with less infarcts strokes
and ventricular tachycardia. Our population
has a prevalence of diabetes mellitus of 18%
or more. Our data is a mirror of the European
population not the U.S.A. Our race is a mixture of European, African and blacks; probably
this mixture makes our people more resistant
to the atherosclerotic factors. At present coronary disease is 20% less than the U.S.A. Probably Puerto Rico is the place on earth more
influenced by U.S.A. culture. 30 years ago
the incidence was 50% less. So that clearly
seen genetics-ethnicity is more important than
diabetes mellitus and hypertension in reducing the cardiovascular events in a population.
Although, we recognize that in our times the
diabetes mellitus and hypertension are crucial
risk factor in the development of heart and atherosclerotic brain disease.
Situational factors have also been reported to
hold relation to the incidence of the metabolic syndrome in Hispanic populations. A cross
sectional analysis that examined associations
between television viewing and the metabolic
syndrome among a representative sample of
Puerto Rican and Dominican elders living in
Massachusetts showed a high prevalence of
the metabolic syndrome that was associated
with prolonged television viewing, independent
of physical activity and energy intake.49 Secondly, a study that evaluated the frequency
of metabolic syndrome and its relationship
with socioeconomic position and education
in women of largely Caribbean Hispanic origin showed an alarming rate of the syndrome
in less educated Caribbean Hispanic women
and was independently associated with lower
education level.50 Although no generalizations
can be from these studies, they shed a definite light on the complexity of the metabolic
syndrome and the connection the human body
holds with the psychological stresses imposed
by the outside world.
Despite the obvious limits of studying a population that does not represent the Hispanic
61
world, further studies considering cardiovascular disease in Puerto Ricans are of utmost
importance in understanding the interrelationship between the genetics, environment and
culture in the modification of cardiovascular
health. Ultimately, the perpetual message continues to be the main point: stronger efforts to
control cardiovascular risk factors and to improve the management of diabetes, hypertension and the other components of the metabolic syndrome are essential in the United States
and Puerto Rico. As clearly seen the Mets syndrome is less aggressive in Puerto Rico than in
the U.S.A., probably this is due to genetics and
cultural aspects, rather than diabetes and hypertension, because the prevalence of both is
greater in Puerto Rico than in the U.S.A. The
prevalence in Puerto Rico is like in Europe.
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Bo, S., Ciccone, G., Baldi, C., et al. Effectiveness of a
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RESUMEN
El síndrome metabólico es una agrupación de factores de riesgo para enfermedad cardiovascular que afecta
un estimado de 50 millones de americanos. El presente artículo repasa el
síndrome metabólico con respecto
a su definición, epidemiología, patofisiología y manejo terapéutico. Un
enfoque investigativo primario ha
sido elucidar los procesos que determinan la resistencia a la insulina, el
mecanismo fundamental que causa el
síndrome metabólico. Estos procesos
son descritos, junto a la interacción
entre el síndrome metabólico con el
sistema de renina-angiotensina, el
ritmo circadiano y la arteriosclerosis.
Finalmente, se introduce la experiencia del síndrome metabólico en el
mundo hispano. Específicamente, se
describen la incidencia, características de componentes y complicaciones del síndrome metabólico en la isla
de Puerto Rico y se sugiere que el síndrome podría ser más leve en Puerto
Rico que en Norteamérica por caracterizarse por menos enfermedad coronariana y un perfil de lípido relativamente normalizado. Esto sugiere que
las complicaciones cardiovasculares
están más influenciadas genética y
culturalmente, que por diabetes mellitus e hipertensión.
63
NEWSLETTER DIGITAL
GRATUITO
EN SU CASILLA DE CORREO ELECTRONICO
CADA MIERCOLES
SUSCRIBASE EN NUESTRO WEBSITE
64
PULMONARY
LYMPHANGIOLEYOMYOMATOSIS:
Literature Update
Samuel Valentín-Mendoza MDa*, José
Nieves-Nieves MDa, Rosángela FernándezMedero MDa, Ricardo Fernández-Gonzales
MDa, José Adorno-Fontánez MDa, Edgardo
Adorno-Fontánez MDb
ABSTRACT
Pulmonary lymphangioleiomyomatosis
is an uncommon disease of unknown
etiology characterized by the proliferation of abnormal smooth muscle cells
in the lungs, leading to parenchymal
destruction and progressive respiratory failure. The natural history of this
disease remains poorly understood,
primarily seen in women of childbearing age. The diagnosis can be difficult
because symptoms are nonspecific
and very similar to other respiratory
diseases like asthma, emphysema
and bronchitis. Lymphangioleiomyomatosis may not be diagnosed until a
pneumothorax, chylothorax, interstitial lung disease or angiomyolipomas
are discovered. The recent advances
in genetic and molecular research provide new hope to discover the intricate
mechanism of disease and evaluate
new therapies. Internists, primary care
physicians and pulmonologists should
be aware of this condition in order to
avoid delay in the diagnosis and institute appropriate therapy. The clinical
features, pathophysiology, molecular
genetics and medical treatment will be
reviewed.
Key words: pulmonary, lymphangioleyomyomatosis, literature, update
INTRODUCTION
Pulmonary Lymphangioleiomyomatosis (LAM)
is characterized as a benign neoplasm with
malignant behavior (mitotic activity, angiolymphatic invasion, necrosis, and metastases) that
unusually occurs in the general population but
mostly affects women of childbearing age.1,2
Clinically, symptoms are nonspecific (see Ta-
Pulmonary Medicine San Juan City Hospital, San Juan Puerto
Rico.
Pulmonary Medicine and Critical Care, VA Caribbean Health
Care Center, San Juan Puerto Rico.
*Corresponding author: Samuel Valentín-Mendoza M - Pulmonary Training Program, San Juan City Hospital, PMB 463 PO
BOX 70344, San Juan, PR 00936. E-mail: samuelvalentinmd@
yahoo.com
a
b
ble I), being dyspnea the most common finding. Hence, it is often misdiagnosed as asthma
or chronic obstructive pulmonary disease due
to the mutual finding of an obstructive impairment on the pulmonary function test.3 Pathophysiologically it is characterized by a proliferation of smooth muscle cells and epitheloid
into lung parenchyma causing a cystic destruction of the lung tissue and subsequently leading to chronic respiratory failure. Radiological
manifestations vary depending on early or the
delayed phase of the disease progress (refer
to Table I), ranging from normal findings to interstitial opacities, hyperinflation, and pleural
effusions. Tissue diagnosis may not always
be necessary to confirm LAM. Nevertheless,
histological findings obtained from open lung
tissue, thoracoscopic biopsy or transbronchial
biopsy in combination with immunohistochemical stains have been employed to improve diagnostic sensitivity and specificity. Prognosis
is variable and the use of supplemental estrogen accelerates the disease progress.
Epidemiology
According to LAM registry data there are approximately 1300 known cases in North America, with Caucasians the racial group mostly
affected.4-8
Clinical Features
The most common presentation in patients
with sporadic LAM is progressive dyspnea and
spontaneous pneumothorax. The first pneumothorax precedes the diagnosis of LAM in
82% of patients, and several studies showed
in fact that most patients have two pneumothoraces before the diagnosis is made.9,10 Other
common complaints (see Table I) which has
been described in the literature include fatigue, cough, wheezing, hemoptysis and chest
pain. Others are related to chylous fluid in the
pleural space and extrapleural location, such
as peritoneum (chylous ascites), pericardium
(chylopercardium), airway (chlyoptysis) and
lung fields develop reticulonodular patterns progressing to cysts, bullae and
honeycombing in the later stages (see
Figures 1 & 2).11 One characteristic feature of chest radiographic findings in LAM
is the preservation of lung volume despite the presence of increased interstitial markings. This finding distinguished
LAM from the other interstitial lung diseases where lung volume is decreased.
High resolution computed tomography
chest scan is more sensitive than conventional radiography in detecting cystic parenchymal disease and is usually
abnormal at the time of diagnosis, even
when the chest x-ray and pulmonary
function assessment are normal.12 The
CT scan shows diffuse, round, bilaterally
thin wall cysts of various sizes ranging
from 1 mm to 45 mm in diameter. Other
features include linear densities (29%),
ground-glass opacities (12%), nodular densities (11%), hilar or mediastinal
lymphadenopathy (9%), pleural effusion,
pneumothorax, lymphangiomata and a
dilated thoracic duct.7
Molecular Biology and Genetics
Though it is not entirely clear how the
pathogenesis of LAM develops, there
have been some associations of several
proteins linked to it.
genitourinary tract (chyluria and chylous metrorrhea). Angiomyolipomas, and less common
the hamartomas may be found in any location
in the chest and abdomen, but mostly seen in
the kidneys.
The physical examination is often nonspecific.
Lung auscultation may reveal crackles in 1520% of patients and rhonchi or wheezing in
less than 15%. Clubbing is uncommon, reported in only 3 to 5% of patients.11 The physical
examination may also reveal ascites, pleural
effusions, pneumothorax, facial angiofibromas, subungual fibromas, palpable dysplastic
cutaneous lesions, hypomelanotic macules
and dental pitting.4
Imaging studies
Radiographic findings are variable (see Table
I). Early in the disease, findings may appear
normal or may show slight hyperinflation with
linear opacities in the lung bases and dorsal
zones. As the clinical condition worsens, the
The tuberin protein is a tumor suppressor and
functions as a key protein in cell growth, proliferation and reorganization of the actin cytoskeleton. This protein is encoded on a tuberous
sclerosis (TSC) locus on chromosome 16p113
(TSC2) and defects on this locus produces a
defective production of the protein leading to
cell proliferation.13,14 Carsillo et. al, reported in
2009 the mutation of TSC2 gene in four patients with abnormal pulmonary smooth muscle cells in the lung tissue which demonstrated
a direct role of TSC2 in the pathogenesis of
this disease15. Though LAM and tuberous
sclerosis are two distinct etiologies it is thought
that patients with LAM are mosaic, with TSC2
mutations in the lung and in some individuals
affecting the kidney as well.15
Role of estrogen – In recent studies estrogen
has been implicated in the pathogenesis of
LAM due to the interaction of signaling between
LAM cells through the Akt pathway which may
play role in cell migration, infiltration, proliferation or secretion of destructive proteases. It
65
66
is suspected that estrogen plays an important
role in the development of the disease since
the pathology is not present before menarche,
rarely manifest after menopause, and is also
known to accelerate during pregnancy and to
abate after oophorectomy. Estrogen and progesterone receptors have been linked to abnormal smooth muscle cells found in abnormal
lung tissue and are found to be up regulated
in the pathogenesis of the disease for which
future studies are directed to down regulate
these receptors by implementing hormonal
therapy.16-18 Until recently, estrogen was shown
to induce pulmonary metastasis and enhance
survival in TSC2 deficient cells in mice.
Metalloproteinase - These proteinases degrade the cellular matrix promoting cell migration. The observations of metalloproteinase
cleavage insulin like growth factor (IGF), which
promote cell growth, suggest that the metalloproteinase stimulate the cell growth via inactivation of IGF binding proteins.19-24
Pathology
Macroscopically, LAM lungs are enlarged and
diffusely cystic with dilated air spaces ranging
from 0.1cm to several centimeters in diameter.25 Microscopically, examination of the lungs
reveals foci of smooth muscle cell infiltration of
the lung parenchyma, airway, lymphatic’s and
blood vessels, associated with areas of thinwalled cystic changes (see Figure 3 to 6). Two
major cell morphologies in LAM lesions are
small spindle-shaped cells and cuboidal epitheloid cells.26 All LAM cells stain positive for
smooth muscle actin, vimentin, and desmenin.
The cuboidal cells within the LAM lesions also
react with monoclonal antibody HMB-45 developed against premelansomal protein gp-100.26
The spindle-shaped cells of LAM lesions are
more frequently proliferating cell nuclear antigen (PCNA) than the cuboidal cells, consistent
with a proliferative phenotype. Estrogen and
progesterone receptors may be also present
in LAM lesions, but not in normal tissue.27 Hemosiderin is common and is a consequence of
clinically insignificant hemorrhage due to ruptured and dilated and tortuous venules.28
Treatment
There are no well-designed studies upon
which to base therapeutic decisions in LAM,
and there is no consensus regarding optimal
treatment of the disease. Since LAM is found
almost exclusively in women, the disease has
been propose to be managed with hormonal
therapy, bilaterally oophorectomy and intramuscular progesterone but these modalities
failed to show improvement and their remains
no proven therapy.29,30
Patients with LAM typically have somatic mutations in hamatin or tuberin. Sirolimus inactivates the rapamycin complex 1 and thus, may
ameliorate LAM. Sirolimus therapy showed
improvement in forced vital capacity, functional residual capacity, and quality of life and
functional performance. However, DlCO and a
6-minute walk did not result in improvement.
The patients also showed stabilization of functional residual capacity and FEV1.31-34
Another important challenge in the treatment
of LAM is the management of the pneumothorax. Pneumothoraces occur in most patients
with LAM and tend to recur, especially after
conservative management. Pleural symphysis
is usually performed in the first pneumothorax,
given the greater than 70% chance of recurrence. Chemical sclerosis, mechanical abrasion, talc poudrage, and pleurectomy have all
been effective in patients with LAM. Management of chylous effusion can include drainage and in some case performed repeatedly.
Pleurodesis may require preventing nutritional
and lymphocyte deficiency from repeated taps
or persistent drainage.34
LAM accounts for 1.1% of lung transplant recipients.35 LAM compares favorably to patients
transplanted for other indications.36-38 The actuarial survival of lung transplantation for LAM
was 86% at 1 year, 76% at 3 years, and 65%
at 5 years.38 The lung function and quality of
life after transplant is improved compared with
patients with advance LAM.37 Both single, and
more commonly, bilateral lung transplantations
have been performed for LAM. Although a bilateral lung transplant is associated with better post-transplant lung function and a reduction in LAM-related complications there is no
difference in survival between the two procedures.35 LAM recurring in the transplanted lung
of either single or bilateral lung transplant is
rare and generally asymptomatic. The main
cause of death after transplant is primary graft
dysfunction, infection and broncholitis obliterans. Despite the overall graft benefit there is
a relatively high rate of disease complications
such as extensive pleural adhesions leading to
moderately severe intraoperative hemorrhage,
pneumothorax in the native lung, postoperative chylothorax and recurrent LAM in the allograft.36
67
Prognosis
Prognosis is variable but progression is common with a median survival of 8-10 year from
diagnosis. Large case series indicated that
38% to 78% of patients are alive at 8.5 years
from the time of the disease onset.9,11 Urban
and associates report a 91% probability of survival at 8.5 years, 70% at 19 years and 71% at
15 years.7 In Japan there have been reports
of 95% survival at 5 years, 89% at 10 years
and 89% at 15 years.39 The large range and
disparity in survival data may reflect the small
numbers of patients with LAM.1,2
Conclusions
Many studies have focused on hormonal aspects of LAM, although the role of estrogens
in the pathogenesis of LAM remains unknown.
Certainly, the mechanism for formation of the
cystic lesions characteristic of LAM will be critical in the development of therapies for LAM.
It is important for clinicians to be familiar with
LAM and new treatments.
REFERENCES
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1998; 114:1689-1703.
2. McCormack FX: lymphangioleiomyomatosis. A clinical update. Chest 2008; 133:507-516.
oleiomyomatosis: A report of 46 patient including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med
1995; 151:527-533.
12. Muller NL, Chiles C, Kulling P: Pulmonary Lymphangioleiomyomatosis. Correlation of CT with radiographic and functional
findings. Radiology 1990; 175: 335-339.
13. Van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome
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14. The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis
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15. Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous
sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci USA 2000;
97: 6085–90.
16. Yu J, Astrinidis A, Howard S, et al. Estradiol and tamoxifen
stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways. Am J
Physiol Lung Cell Mol Physiol 2004; 286: L694–L700.
17. York B, LouD, Panettieri RA Jr, et al. Cross-talk between
tuberin, calmodulin, and estrogen signaling pathways. FASEB J
2005; 19: 1202–1204.
18. Yu JJ, Robb VA, Morrison TA, et al. Estrogen promotes the
survival and pulmonary metastasis of tuberin-null cells. Proc
Natl Acad Sci USA 2009 Feb 24, 106: 2635–2640.
19. Matsui K, Takeda K, Yu ZX, et al. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle
cells in pulmonary lymphangioleiomyomatosis following therapy: an immunohistochemical study. Am J Respir Crit Care Med
2000; 161: 1002–1009.
20. Matsui K, Takeda K, Yu ZX, et al. Role for activation of matrix
metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis. Arch Pathol Lab Med 2000; 124: 267–275.
3. T.B.L. Ho, JH. Hull and N.C. Huges. Eur Respir J 2006;
28:1065-1068.
21. Hayashi T, Fleming MV, Stetler-Stevenson WG, et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and
their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM). Hum Pathol 1997; 28: 1071–1078.
4. Gomez M, Sampson J, Whittermore V (eds): Tuberous Sclerosis Complex (Third edition). Oxford, England: Oxford University Press, 1999.
22. Chilosi M, Pea M, Martignoni G, et al. Cathepsin-K expression in pulmonary lymphangioleiomyomatosis. Mod Pathol
2009; 22: 161–166.
5. Hayasida M, Seyama K, Inoue Y, et al: The epidemiology
of lymphangioleiomyomatosis in Japan: A nationwide cross-sectional study of presenting features and prognosis factors. Respirology 2007; 12:523-530.
23. Bromme D, Okamoto K, Wang BB, et al. Humancathepsin
O2, a matrix protein-degrading cysteine protease expressed in
osteo- clasts. Functional expression of human cathepsin O2 in
Spodoptera frugiperda and characterization of the enzyme. J
Biol Chem 1996; 271: 2126–2132.
6. Johnson SR, Tattersfield AE: Clinical experience of lymphangioleiomyomatosis in the UK. Thorax 2000; 55:1052-1057.
7. Urban T, Lazor R lacronique J, et al: Pulmonary lympahngioleiomyomatosis. A study of 69 patients. Groupe d’etudes
et de Recherche sur les Maladies “Orphelines” Pulmonaires
(GEM”O”P). Medicine (Baltimore) 1999; 78:321-337.
8. Sampson JR, Scahill SJ, Stephenson JB, et al genetic aspects of the tuberous sclerosis in the west of Scotland, J Med
Genet 1989; 26; 28-31.
9. Taylor JR, Ryu J, Colby TV, Raffin TA. Lympahngioleiomyomatosis. Clinical course in 32 patients. N Engl J Med 1990:
323:1254.
10. Almosa KF, Ryu JH, Mendez J, et al: Management of pneumothorax in lynphangioleiomyomatosis: Effects on recurrence
and lung transplantation complications. Chest 129:1274-1281,
2006.
11. Kitaichi M, Nishimura K, Itoh H, et al: Pulmonary lymphangi-
68
24. Merrilees MJ, Hankin EJ, Black JL, et al. Matrix proteoglycans and remodelling of interstitial lung tissue in lymphangioleiomyomatosis. J Pathol 2004; 203: 653–660.
25. Carrington, CB, Cugell DW, Gaensler EA, et al: Lymphangioleiomyomatosis. Physiologic-pathologic-radiologic correlations. Am Rev Respir Dis 1977; 116:977-995.
26. Matsumuto Y, Horiba K, Usuki J, et al: Markers of cell proliferation and expresions of the mealonsomal antigen in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol 1999; 21:327-336.
27. Berger U, Khaghani A, Pomerance A, et al: Pulmonary
lymphangioleiomyomatosis responsive to progesterone and
steroids receptors. An Inmmunocystochemical study. Am J Clin
pathol 11:93:609-614,1990.
28. Kitachi M, Nishimura K, Itoh, Izumi. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including clinic pathologic study of prognosis factors. Am J Repir Crit Care med 1996;
151:527.
RESUMEN
29. Schiavina M, Di Scioscio V, Contini P, et al. Pulmonary
lymphangioleiomyomatosis in karyotipically normalman without tuberous sclerosis complex. Am Respir Crit Care Med
2007,176:96.
La linfangioleiomiomatosis pulmonar es una enfermedad rara de origen desconocido caracterizada por
la proliferación anormal de células de
músculo liso en el pulmón produciendo destrucción de parénquima pulmonar y fallo respiratorio progresivo.
La historia natural de esta enfermedad se desconoce excepto que afecta
principalmente mujeres fértiles. El diagnostico es difícil de hacer porque
los síntomas son inespecíficos y bien
similares a otras enfermedades respiratorias como el asma, enfisema
y la bronquitis. La linfangioleiomiomatosis pulmonar usualmente no se
diagnostica hasta que ocurre un neumotórax, quilotórax, enfermedad intersticial del pulmón o se descubren
angiomiolipomas. Avances recientes
en genética molecular han logrado
descubrir el mecanismo intricado de
esta enfermedad y evaluar nuevas terapias de tratamiento efectivo. Internistas, médicos primarios y neumólogos deben estar al tanto de esta
enfermedad para evitar retrasos en su
manejo y comenzar terapia efectiva
lo antes posible. Las características
clínicas, patofisiología, genética molecular y manejo de esta condición se
revisan en este trabajo.
30. Sieker HO, McCarty Jr KS: Lymphangiomyomatosis: A respiratory illness with an endocrinologic therapy. Trans Am Clin
Climatol Assoc 1987; 99:57-67.
31. Harari S, Cassandro R, Chiodini J, et al: Effect of a gonadotrophin-releasing hormone analogue on lung function in
lymphangioleiomyomatosis. Chest 2008; 133:448-454.
32. De la Fuente J, Paramo C, Roman F, et al: Lymphangioleiomyomatosis: Unsuccessful treatment with luteinizing-hormonereleasing hormone analogues. Eur J Med 1993; 2:377-378.
33. Rossi GA, Balbi B, Oddera S, et al: Response to treatment
with an analog of the luteinizing-hormone-releasing hormone in
a patient with pulmonary lymphangioleiomyomatosis. Am Rev
Respir Dis 1991; 143:174-176.
34. Taveira-Da Silva AM, Hathaway o, Styianou M, Moss J,
Changes in lung function and chylous effusion in patients with
lymphangioleiomyomatosis treated with siroliums. AM Intern
Med 2011;154 (12) :797-805.
35. Trulock EP. Lung transplantation: special considerations and
outcome in LAM. In: Moss J, ed. LAM and other Diseases Characterized by Smooth Muscle Proliferation. New York, Marcel
Dekker, 1999; 65–78.
36. Boehler A, Speich R, Russi EW, et al. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med 1996; 335:
1275–1280.
37. Pechet TT, Meyers BF, Guthrie TJ, et al. Lung transplantation for lymphangioleiomyomatosis. J Heart Lung Transplant
2004; 23: 301–308.
38. Kpodonu J, Massad MG, Chaer RA, et al. The US experience with
lung transplantation for pulmonary lymphangioleiomyomatosis.
J Heart Lung Transplant 2005; 24: 1247–1253.
39. Matsui K, Beasly MB, Nelason WK, et al: Pulmonary significance of pulmonary lymphangioleiomyomatosis histologic
score. Am J surg pathol 2001; 25:479-484.
69
La AMPR concentrará parte de sus esfuerzos en la educación en informática de salud e
investigación y mejoramiento de las técnicas
médicas, como parte de su programa anual de
educación médica continua.
Manténgase informado.
70
VARIACIONES ANATOMICAS DE LA ARTERIA
CAROTIDA INTERNA: IMPLICACIONES PARA EL
TERAPISTA ENDOVASCULAR NEUROLOGICO
Marco Zentenoa, Angel Leeb, Luis Rafael Moscote-Salazarc*
Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”, México.
Hospital Ángeles del Pedregal, México.
c
Departamento de Neurocirugía, Universidad de Cartagena, Cartagenas de Indias, Colombia.
*Autor correspondiente: Dr. Luis Rafael Moscote-Salazar, Universidad de Cartagena, Cartagena de Indias, Colombia.
E-mail: [email protected]
a
b
RESUMEN
La tortuosidad del segmento cervical de la arteria carótida interna (ACI) puede dificultar la
navegación de los dispositivos intravasculares en el tratamiento de aneurismas intracraneales
complejos e incluso técnicas convencionales de acceso ICA pueden fallar. Las variaciones en
el trayecto de la arteria carótida interna son conocidas como ‘coiling’, ‘kinking’ o tortuosidad
del vaso. Este tipo de anomalías puede tener relevancia clínica. Durante procedimientos endovasculares, estas anomalías dificulta la navegación intravascular. Una alternativa potencial
es la reconstrucción de estas anomalías carotideas por métodos neurointervencionistas. Presentamos una reseña práctica de esta literatura.
Palabras índices: variación, anatómica, arteria, carótida, internas, endovascular
INTRODUCCION
Las variaciones anatómicas de la arteria carótida interna son diversas. Este tipo de anomalías puede ser identificadas por estudios ultrasonográficos y por métodos angiográficos.
El segmento cervical de arteria carótida interna (ACI) se extiende desde la bifurcación de
arteria carótida común hasta su entrada en la
base de cráneo, su origen se ubica posterior
o posterolateral a la arteria carótida externa
(ACE), luego asciende posteromedial a este
vaso con un trayecto que puede ser rectilíneo,
curvo o angulado 1,2.
Las anomalías mayores en el segmento cervical de la ACI ocurren cerca de su origen o en
su porción distal a nivel del atlas o del axis.
Weibel, tras realizar 1438 estudios angiográficos de vasos de cuello, encontró que el 75%
de los acodamientos del ACI se ubicaban de 2
a 4 cm. de la bifurcación carotídea3. Estudios
en cadáveres han demostrado la incidencia de
‘Kinking’ carotideo entre un 10 a 40% de la población5, 20.
Por otro lado Weibel define a la tortuosidad
como cualquier ondulación o elongación de
carótida interna en forma de “S” o “C”, mientras que ‘Coiling’ es la elongación o redundancia de la carótida interna con una configuración en ‘S’ exagerada o configuración
circular. Finalmente menciona que el Kinking
(acodamiento) es la angulación de uno o más
segmentos del vaso asociada a estenosis
del segmento afectado3. Leipzig tomando en
cuenta la confusión y la amplia descripción de
términos para describir las irregularidades del
trayecto de la arteria carótida interna dividió
en dos categorías este tipo alteraciones (la
tortuosidad y el acodamiento) de esta manera,
la elongación, redundancia, ondulación configuración en ‘S’ se agrupan como tortuosidades,
de las cuales la gran mayoría no tienen traducción clínica, por otra lado se considera al
acodamiento o kinking como una angulación
aguda del vaso, condición que se considera
adquirida4. La definición más completa es la
de Metz que refiere que el acodamiento de
la ACI se debe a un elongamiento del vaso,
y la define como una angulación abrupta del
eje del vaso de 90º o menos, y a su vez clasificó en tres grados al acodamiento: Grado
1; acodamiento de 90-60º, Grado 2; de 60 a
30º, Grado 3; <30º 5. Nosotros definimos la
tortuosidad de la arteria carótida interna como
cualquier grado de anomalía en la dinámica
del vaso en relación a su morfología normal y
que subyace a una lesión estructural del vaso
carotideo (ver Figura 1).
Definición de conceptos
Tortuosidad: Elongación en forma de S o C u
ondulación en el trayecto de la Arteria carótida
interna
Kinking Leve: Elongación aguda de la Arteria
carótida interna con un Angulo entre los dos
segmentos que forman el kinking mayor a 60
grados.
Kinking moderado: Elongación aguda de la Arteria carótida interna con un ángulo entre los
dos segmentos que forman el kinking entre 30
a 60 grados.
Kinking severo: Elongación aguda de la Arteria
carótida interna con un ángulo entre los dos
segmentos que forman el kinking menor a 30
grados.
Coiling: Elongación o redundancia de la arteria
carótida interna resultando en una configuración extrema en forma de S o en una configuración circular.
Algunos estudios sobre el acodamiento
carotídeo mencionan una prevalencia de 5%
a 25% en los pacientes con síntomas cerebrovasculares o estenosis carotídea asintomática
diagnosticada de forma incidental. Una de
las series más representativas en el estudio
de acodamientos (1000 angiografías) encontró una prevalencia de 16% en una población
hospitalaria que es la más aceptada en la actualidad 6.
De más de 800 casos de tortuosidad y acodamiento ACI estudiados, no existió un predominio en cuanto a sexo, y algunas de estas
anomalías fueron bilaterales7. La prevalencia
de hipertensión arterial en pacientes con acodamiento parece ser mayor que los que no
tienen esta anomalía, Pancera estudió a 590
pacientes con síntomas neurológicos mediante Ultrasonido (USG) Doppler de vasos de
cuello, y encontró una prevalencia de acodamiento de 28.4% en normotensos y de 37.8%
en hipertensos, con una diferencia significativa en ambos grupos (P<0.01)8. Las anormalidades de la arteria carótida interna son
rara vez observadas en niños y en pacientes
jóvenes 20.
El acodamiento de la ACI representa una
condición adquirida, con cambios degenerativos y destrucción de tejido elástico de la pared
vascular, lo que produce una elongación del
vaso y a su vez una acentuación del acodamiento, adicionalmente en cada sístole ex-
iste una elongación momentánea que puede
incrementar el acodamiento4. El acodamiento
de la ACI produce síntomas isquémicos mediante mecanismo tromboembólico y/o hemodinámico, que incluyen cambios en el flujo
por oclusión mecánica asociados a cambios
de posición de la cabeza, microembolización
y éstasis del flujo a nivel del acodamiento9.
El mecanismo hemodinámico cobra importancia mientras mayor sea el grado acodamiento, existen estudios experimentales que
demostraron que el flujo sanguíneo puede reducirse a menos de 40% con un ángulación
de 60º en la ACI y de 60% con una angulación
de 30º.
Los hallazgos histopatológicos en el segmento
angulado son alteraciones primariamente no
inflamatorias y no ateroesclerosas de la capa
media y la íntima. Algunos de estos cambios
son degeneración de la túnica media con fragmentación y desorganización del tejido elástico, hiperplasia de la túnica media, y finalmente
áreas de hiperplasia fibromuscular alternadas
con áreas de adelgazamiento de la media 10,11.
Estudios complementarios en acodamiento carotideo.
La angiografía cerebral ha sido de gran valor
en estos pacientes, y es el patrón de oro para
caracterizar anatómicamente el acodamiento,
se deben obtener proyecciones de cuatro vasos (intracraneales), es importante valorar el
acodamiento en diferentes proyecciones, actualmente con la reconstrucción mediante angiografía 3D se puede medir con exactitud los
grados del acodamiento, los estudios dinámicos como la cineangiografía son útiles para
demostrar las alteraciones hemodinámicas del
acodamiento en el vaso. El retraso en la opacificación de los vasos intracraneales es indicativo de un compromiso importante secundario
al acodamiento.
La técnica de USG Doppler, se basa en el
cambio de frecuencia de un eco emitido por
una fuente de sonido en movimiento, al acercarse a un receptor se observa un incremento
en la frecuencia percibida, y al alejarse un
decremento.
De esta manera es posible determinar la velocidad del flujo sanguíneo basado en el cambio
de frecuencia reflejado por glóbulos rojos en
movimiento con relación a un transductor fijo.
Para la valoración de ACI, es un método seguro, eficaz, no invasivo y de bajo costo. Para
71
la enfermedad carotídea demostró una sensibilidad de 83 a 86% y una especificidad de
89% a 94% para estenosis mayores del 70%,
para el acodamiento ACI igualmente existen
estudios que demostraron su utilidad, aplicando la clasificación de Metz, adicionalmente
dividieron a los que tenían estenosis mayor o
menor de 50%, las velocidades sistólicas en el
acodamiento superiores a 120cm/seg apoyan
el diagnóstico de compromiso hemodinámico
secundario al acodamiento del ACI24.
Opciones Terapéuticas en el acodamiento
carotídeo.
Existen reportes que demuestran que el
acodamiento de la ACI es una condición potencialmente riesgosa, y que el tratamiento
quirúrgico con revascularización ofrece buenos resultados6,11. Algunos estudios concluyeron que en pacientes con insuficiencia
cerebrovascular asociada a acodamiento estenótico, descartando alguna otra causa de la
sintomatología, la corrección del acodamiento
mejora la sintomatología y protege contra la
isquemia cerebral ipsilateral subsecuente6 7,11.
72
El estudio más importante y reciente en el ámbito fue el realizado por Ballota en el que realizó un ensayo clínico en pacientes sintomáticos con elongación ( “coiling” y acodamiento)
de ACI, se aleatorizó a los pacientes tanto al
brazo quirúrgico (n=92) como médico (n=90)
la finalidad determinar infarto y muerte a los
30 días y oclusión tardía. La incidencia de de
AIT tardío hemisférico y retiniano fue significativamente menor en el grupo quirúrgico que
el médico, 7.6% vs 21.1% (P=0.01) y 3.2% vs
12.2% (p=0.03) respectivamente11. Existen
otros pocos reportes que sugieren que el curso clínico del acodamiento carotideo puede
ser benigno. Los síntomas neurológicos transitorios producidos por rotación de la cabeza
es una indicación de peso para el tratamiento
del acodamiento de la ACI. 30
Se describen diferentes técnicas quirúrgicas
para el manejo de acodamientos carotídeo13,41,
a saber:
1) La transposición de arteria, criticado por no
eliminar la elongación arterial.
2) Lisis de adhesiones.
3) Procedimientos vasculares como la resección segmentaria y anastomosis termino- terminal.
4) La técnica de endarterectomía con eversión permite la corrección de elongación severa y acodamiento de la ACI.
Cabe mencionar que todo procedimiento reconstructivo de carótida interna está sujeto a
dificultades técnicas y a complicaciones inher-
interna (ACI) ya sea tortuosidad o acodamientos dificulta la navegabilidad de los catéteres y
en algunos casos impide el acceso adecuado
a la circulación intracraneal a nivel de la lesión
(Ej. Aneurismas), y condiciona a una fracaso
técnico. Adicionalmente, al tratar de forzar el
paso por vasos tortuosos o acodados extracraneales se puede disecar, perforar u ocluir el
vaso. Esto se dificulta más en el caso de utilizar dispositivos adicionales como en la técnica
asistida mediante stent útil en el tratamiento
de aneurismas de cuello ancho (deformabilidad elasticidad) 40,41,41,43,44,45,46,47.
entes a la cirugía.
Angioplastía en enfermedad carotídea.
En la actualidad no existen estudios que aborden el tratamiento de acodamiento mediante
angioplastía con stents. La información disponible sobre angioplastía carotídea proviene
de los realizados por enfermedad carotídea
ateroesclerosa estenótica.
Durante los últimos años la angioplastía carotídea con stent ha sido una alternativa, particularmente en los pacientes con riesgo alto
de complicaciones para la endarterectomía
carotídea21,22,23,24,25,26,27,42.
Los dos aspectos que impulsaron el desarrollo de angioplastía carotídea con stents fueron
la búsqueda de una mejor opción terapéutica
en pacientes de alto riesgo y la tendencia a
realizar cirugía de mínima invasión. Algunos
autores sugieren que este procedimiento es
más seguro, menos traumático y con mejor costo-efectividad que la endarterectomía
carotídea43. Existen varios ensayos clínicos
que han comparado la angioplastía mediante
stent con la endarterectomía carotídea con
resultados similares en cuanto a morbilidad y
mortalidad44,45.
Los procedimientos endovasculares tienen
como riesgo inherente el daño de la íntima y
el riesgo subsecuente de trombosis, agregado
a esto todos los stents son trombogénicos,
por lo tanto, los pacientes que se someten a
stent deben recibir terapia antiplaquetaria. El
clopidrogrel en combinación con la aspirina es
actualmente el tratamiento estándar en los pacientes sometidos a colocación de stent46, 47,48.
Tratamiento aneurismas asociados de acodamientos
La terapia endovascular neurológica ha expandido sus fronteras en el manejo de la patología cerebrovascular, como es el caso de
la oclusión de aneurismas intracraneales. El
abordaje endovascular en general requiere de
la introducción y navegación de microcatéteres
a través de las tortuosidades propias de la circulación intracraneal. Este tipo de técnicas
son adecuadas para el manejo de la patología
aneurismática intracraneal. En el 5 al 14.5%
de aneurismas no es posible la embolización
con ‘coils’ debido a tortuosidad inusual de la
arteria carótida que condiciona un abordaje
problemático. La presencia adicional de irregularidades del trayecto de la arteria carótida
Las tortuosidades carotídeas suelen ser de
origen congénito, pudiendo alcanzar una prevalencia de hasta un 15%, mientras que los
acodamientos que son más bien adquiridos
y ocurren en alrededor 16% de los pacientes
sometidos a angiografías, se ha demostrado
un aumento de la prevalencia de acodamientos asociados a Hipertensión Arterial Sistémica llegando hasta en un 37.8% por lo que no
es infrecuente encontrar la presencia concomitante de A/T y aneurismas intracraneales.
Aspectos del ‘Kinking’
El acodamiento de la ACI representa una
condición adquirida, con cambios degenerativos y destrucción de tejido elástico de la pared
vascular.
El acodamiento de la ACI por si solo puede
ser una entidad patológica, llegando incluso a
producir síntomas isquémicos mediante mecanismo tromboembólico y/o hemodinámico,
que incluyen cambios en el flujo por oclusión
mecánica asociados a cambios de posición
de la cabeza, microembolización y éstasis del
flujo a nivel del acodamiento9. El mecanismo
hemodinámico cobra importancia mientras
mayor sea el grado acodamiento, existen estudios experimentales que demostraron que el
flujo sanguíneo puede reducirse a menos de
40% con un angulación de 60º en la ACI y de
60% con una angulación de 30º.
El manejo actual de los acodamientos y tortuosidades es controversial. Existe alguna
evidencia de que el manejo quirúrgico de
estas lesiones, en el caso de pacientes con
síntomas isquémicos puede ser beneficiosa.
Existen diversas técnicas quirúrgicas, muchas
consisten en la resección del segmento angulado, considerando en un principio a estos
no aptos para la corrección mediante angioplastía con stent, por la presencia de adherencias externas. Nuestro grupo ha logrado
73
reconstruir de manera exitosa mediante técnicas endovasculares anomalías anatómicas de
la arteria carótida intracraneal, en la mayoría
con la resolución completa el kinking. Tres
pacientes presentaron un ”escalón” o tortuosidad transmitida distal al stent, que no tuvieron significancia o obstaculizaron el abordaje.
Según nuestra experiencia esto se minimiza
asegurando que el despegamiento del primer
stent se inicie en la unión de arteria carótida
cervical y petrosa, y extendiéndose hasta
ACC, requiriendo para esto en general dos
stents carotídeos telescopados (ver Figura 2)
32,33,33,34,35,36,37,38
.
El tratamiento de las anomalías anatómicas
de la carótida interna es un tema muy interesante, el manejo integral por parte de terapistas endovasculares, neurólogos vasculares y
neurocirujanos es fundamental para una decisión terapéutica acertada.
CONCLUSIONES
Las anormalidades en la geometría y en los
trayectos de la arteria carótida interna son
comúnmente identificadas en ultrasonografía
y estudios angiográficos. La clasificación como
tortuosidad, kinking y coiling fue introducida en
1965 por Weibel y Fields . Esta clasificación
propone que la tortuosidad es una elongación
en forma de S o C en el trayecto de la arteria
carótida interna. Finalmente sugerimos que la
corrección de acodamientos carotideos mediante angioplastía con stent facilita el abordaje
endovascular en especial para el tratamiento
de aneurismas complejos (gigantes y/o de
cuello ancho) mejorando la navegabilidad de
los stents IC y la mejor maniobrabilidad de los
microcatéteres para embolización de aneurismas.
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75
ABSTRACT
Tortuosity of the cervical segment of the internal carotid artery (ICA) can hinder navigation intravascular devices for treating
intracranial aneurysms and even complex
ICA access techniques can fail. Variations
in the course of the internal carotid artery
are known as coiling, kinking or tortuosity
of the vessel. Such failures have clinical
relevance. During endovascular procedures these anomalies difficult the intravascular surgical procedure. A potential
alternative is the reconstruction of these
anatomic anomalies of the carotid artery
using neuro-interventional methods. We
present a practical review of the literature.
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