Background: Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular
disease that is usually not mentioned in multicenter registries on all-type acute
stroke. We aimed to describe the experience on hospitalized patients with CVT in
a Mexican multicenter registry on acute cerebrovascular disease. Methods: CVT
patients were selected from the RENAMEVASC registry, which was conducted
between 2002 and 2004 in 25 Mexican hospitals. Risk factors, neuroimaging,
and 30-day outcome as assessed by the modified Rankin scale (mRS) were analyzed.
Results: Among 2000 all-type acute stroke patients, 59 (3%; 95% CI, 2.3-3.8%) had
CVT (50 women; female:male ratio, 5:1; median age, 31 years). Puerperium (42%),
contraceptive use (18%), and pregnancy (12%) were the main risk factors in women.
In 67% of men, CVTwas registered as idiopathic, but thrombophilia assessment was
suboptimal. Longitudinal superior sinus was the most frequent thrombosis location
(78%). Extensive (.5 cm) venous infarction occurred in 36% of patients. Only 81% of
patients received anticoagulation since the acute phase, and 3% needed decompressive
craniectomy. Mechanical ventilation (13.6%), pneumonia (10.2%) and systemic
thromboembolism (8.5%) were the main in-hospital complications. The 30-day case
fatality rate was 3% (2 patients; 95% CI, 0.23-12.2%). In a Cox proportional hazards
model, only age ,40 years was associated with a mRS score of 0 to 2 (functional independence;
rate ratio, 3.46; 95% CI, 1.34-8.92). Conclusions: The relative frequency
of CVT and the associated in-hospital complications were higher than in other registries.
Thrombophilia assessment and acute treatment was suboptimal. Young age
is the main determinant of a good short-term outcome.
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Cerebral Venous Thrombosis in a Mexican Multicenter Registry of Acute Cerebrovascular Disease: The RENAMEVASC Study
1. Cerebral Venous Thrombosis in a Mexican Multicenter Registry
of Acute Cerebrovascular Disease: The RENAMEVASC Study
Jos L. Ruiz-Sandoval, MD,*† Erwin Chiquete, MD, PhD,*
e
~
L. Jacqueline Banuelos-Becerra, MD,‡ Carolina Torres-Anguiano, MD,‡
Christian Gonzlez-Padilla, MD,‡ Antonio Arauz, MD,x
a
Carolina Leon-Jimnez, MD,k Luis M. Murillo-Bonilla, MD, MSc,**
e
Jorge Villarreal-Careaga, MD,†† Fernando Barinagarrementer MD,‡‡
ıa,
Carlos Cant -Brito, MD, PhD xx and the RENAMEVASC investigatorskk
u
Background: Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular
disease that is usually not mentioned in multicenter registries on all-type acute
stroke. We aimed to describe the experience on hospitalized patients with CVT in
a Mexican multicenter registry on acute cerebrovascular disease. Methods: CVT
patients were selected from the RENAMEVASC registry, which was conducted
between 2002 and 2004 in 25 Mexican hospitals. Risk factors, neuroimaging,
and 30-day outcome as assessed by the modified Rankin scale (mRS) were analyzed.
Results: Among 2000 all-type acute stroke patients, 59 (3%; 95% CI, 2.3-3.8%) had
CVT (50 women; female:male ratio, 5:1; median age, 31 years). Puerperium (42%),
contraceptive use (18%), and pregnancy (12%) were the main risk factors in women.
In 67% of men, CVT was registered as idiopathic, but thrombophilia assessment was
suboptimal. Longitudinal superior sinus was the most frequent thrombosis location
(78%). Extensive (.5 cm) venous infarction occurred in 36% of patients. Only 81% of
patients received anticoagulation since the acute phase, and 3% needed decompressive craniectomy. Mechanical ventilation (13.6%), pneumonia (10.2%) and systemic
thromboembolism (8.5%) were the main in-hospital complications. The 30-day case
fatality rate was 3% (2 patients; 95% CI, 0.23-12.2%). In a Cox proportional hazards
model, only age ,40 years was associated with a mRS score of 0 to 2 (functional independence; rate ratio, 3.46; 95% CI, 1.34-8.92). Conclusions: The relative frequency
of CVT and the associated in-hospital complications were higher than in other registries. Thrombophilia assessment and acute treatment was suboptimal. Young age
is the main determinant of a good short-term outcome. Key Words: Cerebral veins—
cerebral venous thrombosis—cerebrovascular disease—cranial sinuses—outcome—
stroke.
Ó 2012 by National Stroke Association
From the *Department of Neurology, Hospital Civil de Guadalajara
‘‘Fray Antonio Alcalde,’’, †Department of Neurosciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara,
‡Department of Internal Medicine, Hospital Civil de Guadalajara
‘‘Fray Antonio Alcalde,’’ Guadalajara, Mexico, xStroke Clinic, Instituto Nacional de Neurolog y Neurociruga, Mexico City, Mexico,
ıa
ı
kDepartment of Neurology, Hospital Valentn Gmez Far Zapoı
o
ıas,
pan, Mexico, **Endovascular Therapy, Instituto Panvascular de Occidente and Universidad Autnoma de Guadalajara, Guadalajara,
o
Mexico, ††Department of Neurology, Hospital General de Culiacn,
a
Culiacn, ‡‡Hospital Angeles Quertaro, Quertaro, xxInstituto Naa
e
e
cional de Ciencias Mdicas y Nutricin ‘‘Salvador Zubirn,’’ Mexico
e
o
a
City, Mexico; and kkRENAMEVASC investigators are listed in the Appendix.
Received May 2, 2010; revision received December 23, 2010;
accepted January 13, 2011.
Address correspondence to Jos L. Ruiz-Sandoval, MD, Servicio de
e
Neurologa y Neurocirug Hospital Civil ‘‘Fray Antonio Alcalde,’’
ı
ıa,
Hospital 278, 44280 Guadalajara, Jalisco, Mexico. E-mail:
jorulej-1nj@prodigy.net.mx.
1052-3057/$ - see front matter
Ó 2012 by National Stroke Association
doi:10.1016/j.jstrokecerebrovasdis.2011.01.001
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 5 (July), 2012: pp 395-400
395
2. J.L. RUIZ-SANDOV
AL ET AL.
396
Cerebral venous thrombosis (CVT) is the least common
form of acute cerebrovascular disease,1 accounting for
about 0.5% among all types of strokes.2 Depending on
the population and methodology, the estimated annual incidence ranges from 1 to 12 cases per million adults per
year,3-6 and about 7 cases per million children (especially
neonates) per year.7 Although generally considered a condition with a very good outcome in developed countries,
the case fatality rate during the hospitalization period
may surpass 15% in low-income nations, especially associated with a delay in diagnosis and with low anticoagulation practice.6,8-10
In Mexico, information regarding CVT has mainly derived from single-center reports, with a relative frequency
among all forms of acute cerebrovascular disease ranging
from 0.43% to 8%.11-13 There is a paucity of international
epidemiologic data on incidence, prevalence, or relative
frequency among hospitalized stroke patients, and
hospital registers on all-type acute stroke cases rarely refer
specifically to CVT.14,15 The National Mexican Registry
of Cerebral Vascular Disease (RENAMEVASC) was a
multicenter stroke surveillance system that included
2000 consecutive patients with all types of acute
cerebrovascular disease,16,17 of whom 59 were identified
with CVT. The aim of this report on CVT is to describe
the risk factors, neuroimaging features, acute
management, in-hospital complications, and the 30-day
outcomes of CVT patients hospitalized in Mexico.
Methods
Patients
This prospective, hospital-based multicenter registry
was conducted between November 2002 and October
2004 in 25 referral centers from 14 states of Mexico. All investigators were neurologists trained in cerebrovascular
disease. The complete methodology of the RENAMEVASC study has been reported elsewhere.16,17 Briefly,
consecutive patients were registered if a suspected acute
cerebrovascular disease was confirmed and accurately
classified by computed tomographic (CT) or magnetic
resonance imaging (MRI) scanning in all patients. A
standardized case report form was used to collect
clinical data from the patient or primary guardian. The
patient’s functional status was classified by the
modified Rankin scale (mRS). For the purpose of this
report, patients with CVT confirmed by MRI, MRI
venography, or four-vessel angiography were included.
The coordinating office performed the case ascertainments. The internal committee of ethics of every participating center approved the present study. Informed
consent was obtained from the patient or the legal proxy.
Data Analysis
For the main relative frequencies reported, 95% confidence intervals (CIs) were calculated using the adjusted
Wald method. Pearson Chi-square or Fisher exact tests
were used to assess proportions in nominal variables for
bivariate analyses. To compare quantitative variables between 2 groups, the Student t and Mann–Whitney U tests
were performed in distributions of parametric and nonparametric variables, respectively. A Cox proportional
hazards model was constructed to find independent predictors of 30-day functional independence (mRS, 0-2).
Competing variables were chosen with a P set at , .1 in
the bivariate selection process. Adjusted rate ratios (RRs)
with the respective 95% CIs are provided. A Kaplan–Meier
actuarial analysis was performed to evaluate the association of the independent predictors with a good functional
outcome (mRS, 0-2) during the follow-up. P values are
2-sided and considered significant when P , .05. SPSS
for Windows (version 17.0; SPSS, Chicago, IL) was used
in all calculations.
Results
The RENAMEVASC registry included 2000 hospitalized patients with all types of acute cerebrovascular disease. In all, 59 (2.97%; 95% CI, 2.3-3.8%) had CVT. There
were 50 (85%) women and 9 (15%) men (female:male ratio, 5:1), with a median age of 31 years (interquartile
range, 22-39 years). A total of 45 (76%) patients were
younger than 40 years of age. The median time from neurologic symptoms to hospital presentation was 48 hours
(interquartile range, 15-96 hrs). Only 1 case of CVT was
identified during hospital stay for another cause. Table 1
shows the main risk factors and clinical presentation associated with CVT, stratified by gender and age. Puerperium and oral contraceptives use were the most
frequent risk factors (in the female gender separately,
42% and 18%, respectively). Only 1 of 21 (4.7%) women
in puerperium had severe concomitant anemia (hemoglobin concentration ,7 g/dl), and only one patient (a 57year-old woman) had this factor as the unique etiology
of CVT. As expected, puerperium was more frequent
among young women than their older counterparts
(51.2% v 0%); however, no differences on contraceptive
use were observed when comparing women aged ,40
years of age with older females (17.1% v 22.2%; P 5 .66).
CVT was associated with pregnancy in 6 (14.5%) women.
Among all patients, a previous major surgery in the last
15 days was more frequently observed in people $40 years
of age than in younger patients (P 5.009). No cases associated with malignancy were identified. There were no assessments for hereditary thrombophilia in this cohort.
At hospital arrival, 33 (56%) patients were alert, 21
(36%) drowsy, 3 (5%) stuporous, and 2 (3%) in coma.
The mean Glasgow coma score at hospital presentation
was 13.5 points (range, 3-15 points; median, 14; interquartile range, 13-15 points). Headache and nausea/vomiting
were more frequent in women than in men, whereas motor deficit was more common in the male gender (Table 1).
3. CEREBRAL VENOUS THROMBOSIS IN MEXICO
397
Table 1. Analysis of risk factors and clinical presentation of cerebral venous thrombosis
Gender, n (%)
Age, n (%)
All patients
(n 5 59)
Variables
Risk factors,* n (%)
Puerperium
Oral contraceptives
Major surgery in the last 15 days
Pregnancy
Current smoking
Severe anemia
Migraine
Clinical presentation, n (%)
Headache
Seizures
Nausea/vomiting
Altered mental status
Focal motor deficit
Impaired speech
Male
(n 5 9)
Female
(n 5 50)
Py
,40 y
(n 5 45)
$40 y
(n 5 14)
Pz
21 (35.6)
9 (15.3)
6 (10.2)
6 (10.2)
5 (8.5)
4 (6.9)
2 (3.4)
0
0
2 (22.2)
0
1 (11.1)
1 (11.1)
0
21 (42.0)
9 (18.0)
4 (8.0)
6 (12.0)
4 (8.0)
3 (6.1)
2 (4.0)
.01
.17
.20
.27
.76
.50
.99
21 (46.7)
7 (15.6)
2 (4.4)
6 (13.3)
3 (6.7)
2 (4.5)
2 (4.4)
0
2 (14.3)
4 (28.6)
0
2 (14.3)
2 (14.3)
0
.001
.90
.009
.15
.37
.21
.99
54 (91.5)
12 (20.3)
34 (57.6)
28 (47.5)
10 (16.9)
12 (20.3)
6 (66.7)
0
1 (11.1)
4 (44.4)
4 (44.4)
0
48 (96.0)
12 (24.0)
33 (66.0)
24 (48.0)
6 (12.0)
12 (24.0)
.02
.18
.003
.99
.04
.18
43 (95.6)
10 (22.2)
27 (60.0)
20 (44.4)
7 (15.6)
1 (2.2)
11 (78.6)
2 (14.3)
7 (50.0)
8 (57.9)
3 (21.4)
3 (21.4)
.08
.71
.51
.41
.69
.04
*No risk factors were identified in 6 (66.7%) male patients.
yP value for differences between men and women; Chi-square or Fisher exact test as appropriate.
zP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.
Brain imaging studies showed extensive venous infarction (length .5 cm) or edema in 21 (36%) patients and
bihemispheric infarction in 13 (22%; Table 2). Longitudinal superior sinus was the most frequent location of
CVT (78% of patients), followed by the lateral sinus in 9
(15%) cases. No differences were observed according to
gender or age groups with respect to CVT location, extension, or in-hospital complications.
Mean in-hospital stay was 16.8 days (range, 3-57 days);
being significantly higher among older patients than in
younger individuals (24.1 v 14.6 days, respectively; P 5
.005). Mechanical ventilation and hospital-acquired pneumonia were more frequent in patients $40 years of age
than in younger individuals (Table 3). It is noteworthy
that systemic thromboembolism occurred during hospital
stay in 8% of cases (1 case resulting in death) without
differences between genders or age groups. A total of
48 (81%) patients received anticoagulation in the acute
stage, with intravenous heparin being the most frequent
method (46%) followed by low-molecular-weight heparin
(LMWH; 31%) and oral coumarins (5%). Two (3%) patients
underwent craniectomy (Table 2).
In all, 37 (63%) patients attained functional independence (mRS, 0-2) at hospital discharge, 20 (34%) were dependent, and 2 (3%; 95% CI, 0.23-12.2%) died (Table 4).
Of the 2 fatalities registered, 1 was attributed to a neurologic etiology (a women in puerperium with longitudinal
sinus thrombosis, severe hemorrhagic venous infarction,
Table 2. Radiologic features of patients with cerebral venous thrombosis
Gender, n (%)
Age, n (%)
Variables
All patients
(n 5 59)
Male
(n 5 9)
Female
(n 5 50)
P*
,40 y
(n 5 45)
$40 y
(n 5 14)
Py
Radiologic features, n (%)
Extensive venous infarction (.5 cm)
Bihemispheric venous infarction
Longitudinal superior
Lateral
Straight sinus
Cortical veins
21 (35.6)
13 (22.0)
46 (78.0)
9 (15.3)
2 (3.4)
2 (3.4)
3 (33.3)
2 (22.2)
6 (66.7)
3 (33.3)
0
2 (4.0)
18 (36.0)
11 (22.0)
40 (80.0)
6 (12.0)
2 (4.0)
0
.88
.99
.37
.10
.99
.99
16 (35.6)
10 (22.2)
34 (75.6)
8 (17.8)
2 (4.4)
1 (2.2)
5 (35.7)
3 (21.4)
12 (85.7)
1 (7.1)
0
1 (7.1)
.99
.95
.42
.33
.99
.42
*P value for differences between men and women; Chi-square or Fisher exact test as appropriate.
yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.
4. J.L. RUIZ-SANDOV
AL ET AL.
398
Table 3. In-hospital management and complications in patients with cerebral venous thrombosis
Gender, n (%)
Age, n (%)
Variables
All patients
(n 5 59)
Male
(n 5 9)
Female
(n 5 50)
P*
,40 y
(n 5 45)
$40 y
(n 5 14)
Py
Complications, n (%)
Mechanical ventilation
Hospital-acquired pneumonia
DVT/pulmonary embolism
Urinary tract infections
Acute management, n (%)
Intravenous heparin
LMWH at therapeutic dosage
LMWH at prophylactic dosage
Oral anticoagulant therapy
Antiplatelets
Steroids
Craniectomy
8 (13.6)
6 (10.2)
5 (8.5)
2 (3.4)
57 (96.6)
27 (45.8)
11 (18.6)
7 (11.9)
3 (5.1)
7 (11.9)
1 (1.7)
2 (3.4)
2 (22.2)
2 (22.2)
1 (11.1)
0
8 (88.9)
3 (33.3)
2 (22.2)
1 (11.1)
0
2 (22.2)
0
0
6 (12.0)
4 (8.0)
4 (8.0)
2 (4.0)
49 (98.0)
24 (48.0)
9 (18.0)
6 (12.0)
3 (6.0)
5 (10.0)
1 (2.0)
2 (4.0)
.41
.19
.76
1
.28
.42
.76
.94
.99
.29
.99
.99
3 (6.7)
1 (2.2)
4 (8.9)
1 (2.2)
45 (100)
24 (53.3)
7 (15.6)
5 (11.1)
2 (4.4)
6 (13.3)
0
1 (2.2)
5 (35.7)
5 (35.7)
1 (7.1)
1 (7.1)
12 (85.7)
3 (21.4)
4 (28.6)
2 (14.3)
1 (7.1)
1 (7.1)
1 (7.1)
1 (7.1)
.006
.001
.84
.42
.05
.04
.27
.74
.56
.99
.24
.42
Abbreviations: DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin.
*P value for differences between men and women; Chi-square or Fisher exact test as appropriate.
yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.
and coma at hospital presentation) and the other as of systemic cause (a women with hypothyroidism who develop
massive pulmonary thromboembolism, is spite of anticoagulation with LMWH). At 30 days of follow-up, 43 (73%)
patients were independent and 14 (24%) remained
functionally dependent for activities of daily living. No
further deaths were registered at 30 days (Table 4). In
a Cox proportional hazards model adjusted for gender,
Glasgow coma scale at admission, in-hospital pneumonia,
and systemic thromboembolism, only age , 40 years was
independently associated with a good 30-day outcome
(RR, 3.46; 95% CI, 1.34-8.92; Fig 1). Time from CVT onset
to hospital presentation was not independently associated
with a good or adverse outcome.
Discussion
The RENAMEVASC study is the first collaborative,
nongovernmental, non–industry sponsored registry on
patients hospitalized with all-type acute cerebrovascular
disease. In this registry, we observed 3% of cases with
CVT among all stroke types. In other countries, the relative frequency ranges from 0.5% to 2%.2,5,9,10 However,
in autopsy studies, CVT has been observed in a relative
frequency of as much as 10%,19 which suggests that
CVT is often clinically overlooked. Here we observed
a very high female:male ratio, possibly because of
selection bias and to a high proportion of genderspecific risk factors. For comparison, in the ISCVT
Table 4. Outcome at hospital discharge and at 30-day follow-up in patients with cerebral venous thrombosis
Gender, n (%)
Variables
mRS at discharge, n (%)
0-2
3-5
6
mRS at 30-day follow-up
0-2
3-5
6
Age, n (%)
All patients
(n 5 59)
Male
(n 5 9)
Female
(n 5 50)
P*
,40 y
(n 5 45)
$40 y
(n 5 14)
Py
37 (62.7)
20 (33.9)
2 (3.4)
3 (33.3)
6 (66.7)
0
34 (68.0)
14 (28.0)
2 (4.0)
.05
.02
.99
34 (75.6)
10 (22.2)
1 (2.2)
3 (21.4)
10 (71.4)
1 (7.1)
,.001
.001
.42
43 (72.9)
14 (23.7)
2 (3.4)
6 (66.7)
3 (33.3)
0
37 (74.0)
11 (22.0)
2 (4.0)
.65
.46
.99
38 (84.4)
6 (13.3)
1 (2.2)
5 (35.7)
8 (57.1)
1 (7.1)
,.001
.001
.42
Abbreviation: mRs, modified Rankin score.
*P value for differences between men and women; Chi-square or Fisher exact test as appropriate.
yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.
5. CEREBRAL VENOUS THROMBOSIS IN MEXICO
Figure 1. Kaplan–Meier actuarial analyses on the probability of achieving
a modified Rankin scale score of 0 to 2 (functional independence) during the
follow-up period, as a function of age , 40 years (n 5 45) or older (n 5 14).
registry, roughly 75% of patients were women (a 3:1
female:male ratio).20 In most international studies, the
main risk factors for CVT are thrombophilia, oral contraceptive use, infections, pregnancy, puerperium, and malignancy.9,10,18,20-24 In our study, gender-specific risk
factors explained the majority of cases. This differs greatly
from registries conducted in developed countries,20,23
where a systematic search for thrombophilia and an
active seeking of patients from the oncology and
hematology wards is performed. CVT is a consequence
of multiple factors, and the identification of one of them
should not prevent the intentional search for coexisting
causes1 that may potentially increase the probability of recurrence.25-27 In the ISCVTregistry, 44% of the patients had
.1 risk factor, and congenital or genetic thrombophilia
was present in 22% of patients.20 A gender-specific risk factor was present in 65% women.20
A case fatality rate of 3% was observed in our
registry, considerably lower than other studies that
report rates from about 6% to as high as 27% in elderly
patients.8-10,20,28,29 Indeed, this could represent a survival
bias of our study; nevertheless, this low case fatality rate
occurred at expense of a relatively high frequency of
cases with severe disabilities and numerous short-term
(mainly in-hospital) complications. In-hospital systemic
thromboembolism was observed in 8% of our cases. An
early literature review (1942-1990) performed by Diaz
et al.30 revealed that 11% of CVT cases were associated
with pulmonary embolism, and among these patients,
the overall mortality rate was 96%. In a recent report on the
ISCVT cohort, 6% of cases had systemic thromboembolism.31 This discrepancy between ours and the ISCVT registry with respect to systemic venous thromboembolism
parallels the different frequency of full anticoagulation in
the acute phase of management (64% v 83% in the
RENAMEVASC and ISCVT registries, respectively).20
399
This important finding emphasizes the need for anticoagulation at therapeutic doses as soon as CVT is identified.1,32
The main limitation of this report is the small sample
size, which prevents an accurate detection of small, but
clinically meaningful differences, especially in outcome
analyses. Long-term follow-up was not registered, and
as a consequence, other important complications, such as
neuropsychological impairment and CVT recurrence,
could not be analyzed. Nevertheless, this study may provide important information for comparative epidemiology
that may potentially improve deliver of care in Mexico.
In conclusion, this multicenter registry showed that the
relative frequency of CVT in hospitalized cerebrovascular
patients in Mexico is higher than expected. Acute case
fatality rate is relatively low, but numerous in-hospital
short-term complications occurred. Acute management
with therapeutic anticoagulation was suboptimal and
may potentially account for the high rate of systemic
thromboembolism observed in this registry.
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Appendix
The RENAMEVASC Investigators
Steering committee: C. Cant -Brito, A. Arauz-Gngora, J.L.
u
o
Ruiz-Sandoval, J. Villarreal-Careaga, L. Murillo-Bonilla,
R. Rangel-Guerra, and F. Barinagarrementeria.
Coordinating office: C. Cant -Brito and L. Murillo-Bonilla.
u
Participants: The following centers and investigators participated in the RENAMEVASC study: C. Cant -Brito
u
(Instituto Nacional de Ciencias Mdicas y Nutricin Salvae
o
dor Zubirn, Ciudad de Mxico); A. Arauz-Gngora,
a
e
o
L. Murillo-Bonilla, and L. Hoyos (Instituto Nacional de
Neurolog y Neurocirug Ciudad de Mxico). J.L.
ıa
ıa,
e
Ruiz-Sandoval and E. Chiquete (Hospital Civil de Guadalajara, Jalisco); J. Villarreal-Careaga and F. Guzmn-Reyes
a
(Hospital General de Culiacn, Sinaloa); F. Barinagarrea
menteria (Hospital Angeles de Quertaro, Quertaro);
e
e
J.A. Fernndez (Hospital Jurez, Ciudad de Mxico);
a
a
e
B. Torres (Hospital General de Len, Guanajuato);
o
C. Len-Jimnez (Hospital General ISSSTE, Zapopan,
o
e
Jalisco); I. Rodr
ıguez-Leyva (Hospital General de San
Luis Potos San Luis Potosi): R. Rangel-Guerra (Hospital
ı,
Universitario de Nuevo Len, Monterrey, Nuevo Len);
o
o
M. Ba~ os (Hospital General de Balbuena, Ciudad de
n
Mxico); L. Espinosa and M. de la Maza, Hospital San
e
Jos de Monterrey, Nuevo Len); H. Colorado (Hospital
e
o
General ISSSTE, Veracruz, Veracruz); M.C. Loy-Gerala
(Hospital General de Puebla, Puebla); J. Huebe-Rafool
(Hospital General de Pachuca, Hidalgo); G. Aguayo Leytte
(Hospital General de Aguascalientes, Aguascalientes);
G. Tavera-Guittings (Hospital General ISSSTE, Campeche,
Campeche); V. Garcia-Talavera (Hospital IMSS ‘‘La Raza,’’
Ciudad de Mxico); O. Ibarra and M. Segura (Hospital
e
General de Morelia, Morelia); J.L. Sosa (Hospital General
de Villahermosa, Tabasco); O. Talams-Murra (Hospital
a
General ISSSTE, Torren, Coahuila); M. Alanis-Quirga
o
o
(Hospital Universitario de Torren, Coahuila); J.M. Escao
milla (Hospital de la Marina Nacional, Ciudad de Mxico);
e
M.A. Alegr (Hospital Central Militar, Ciudad de
ıa
Mxico); and J.C. Angulo (Hospital General, Veracruz,
e
Veracruz).