Papers by Marielle Esteves

Journal of Laparoendoscopic & Advanced Surgical Techniques, 2016
Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures i... more Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α). Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed. CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections. This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.

Surgical Endoscopy, 2013
This study aimed to assess the feasibility of single-access fetal endoscopy (SAFE) for the manage... more This study aimed to assess the feasibility of single-access fetal endoscopy (SAFE) for the management of myelomeningocele (MMC) using intrauterine carbon dioxide as a distension medium in a sheep model. This prospective experimental case-control study investigated 12 lamb fetuses that had a myelomeningocele-like defect surgically created on the 75th day of gestation. Four fetuses remained untreated (control group), and eight fetuses had MMC repair using two fetoscopic approaches with carbon dioxide used to distend the amniotic cavity. A collagen patch was placed over the defect and secured with surgical sealant. Four animals had a two-port fetoscopic procedure, and four animals had SAFE. Clinical and pathologic studies were performed after delivery. This study confirmed the validity of the animal MMC model. None of the control animals was able to stand or walk, and all had a significant defect in the lumbar area with continuous leakage of cerebrospinal fluid, ventriculomegaly, and a Chiari-II malformation. All the treated animals, independently of the number of ports used in the repair, were able to walk and had a closed defect with resolution of the Chiari malformation. The SAFE patch and glue coverage of surgically created fetal MMC is feasible and effective in restoring gross neurologic function in the fetal lamb model.

Journal of Pediatric Orthopaedics, 2009
Extremity amniotic band (EAB) syndrome can cause an intrauterine amputation as a result of a mech... more Extremity amniotic band (EAB) syndrome can cause an intrauterine amputation as a result of a mechanical effect with progressive strangulation. The aim of the study is to assess the use of fetal surgery of EABs with risk of amputation in the ovine fetus. Right limbs of fifteen 60-day-gestational age fetal sheep were ligated with silk suture at the infracondylar level. Left limbs were used for paired comparison. Fetuses were randomized into 3 groups: an early-repair group (n = 5), a late-repair group (n = 5), and a nonrepaired group (n = 5). The limbs of the 2 repaired groups underwent fetal release. The limbs obtained from at-term fetuses were analyzed morphologically, functionally, and radiologically. Statistical analysis with paired test was used to compare data. Nonrepaired limbs showed amputation or quasi amputation; the repaired ones did not. However, those late-repaired had significantly reduced passive ankle range of motion, shorter limb length, and mild residual changes. Intrauterine release of potentially severe EABs prevents limb amputation and leads to morphofunctional recovery. Early release shows better results. : Intrauterine amputations caused by EABs in the human fetus might be avoidable by fetal surgery.

Cancer Research, 2009
Colorectal cancer is the second cause of cancer-related death in the western world, and although ... more Colorectal cancer is the second cause of cancer-related death in the western world, and although the genetic and molecular mechanisms involved in the initiation and progression of these tumors are among the best characterized, there are significant gaps in our understanding of this disease. The role of EPHB signaling in colorectal cancer has only recently been realized. Here, we use animal models to investigate the role of EphB4 in intestinal tumorigenesis. Modulation of EPHB4 levels in colon cancer cell lines resulted in significant differences in tumor growth in a xenograft model, with low levels of EPHB4 associated with faster growth. In addition, using a genetic model of intestinal tumorigenesis where adenomatous polyposis coli (Apc) mutations lead to initiation of the tumorigenic process (Apc min mice), we show that inactivation of a single allele of EphB4 results in higher proliferation in both the normal epithelium and intestinal tumors, significantly larger tumors in the small intestine, and a 10-fold increase in the number of tumors in the large intestine. This was associated with a 25% reduction in the lifespan of Apc min mice (P < 0.0001). Gene expression analysis showed that EphB4 mutations result in a profound transcriptional reprogramming, affecting genes involved in cell proliferation, remodeling of the extracellular matrix, and cell attachment to the basement membrane among other functional groups of genes. Importantly, in agreement with the expression profiling experiments, using an in vitro assay, we show that loss of EPHB4 in colon cancer cells results in a significantly increased potential to invade through a complex extracellular matrix. Collectively, these results indicate that EphB4 has tumor suppressor activities and that regulation of cell proliferation, extracellular matrix remodeling, and invasive potential are important mechanisms of tumor suppression.

Pediatric emergency care, Jan 14, 2015
The objective of this study was to evaluate the efficacy of a short hands-on chest ultrasound cou... more The objective of this study was to evaluate the efficacy of a short hands-on chest ultrasound course to detect normal lung pattern, pneumothorax (PTX), and pleural effusion (PE) in a porcine animal model. Thirty-six trainees with no previous experience in chest ultrasound participated in the study. A 1.5-hour training course covering both theory and practice was developed. All static and dynamic signs of the normal lung parenchyma, PTX, and PE were analyzed. Four pigs were used. Approval by the local institutional animal care was obtained. An 8F drainage catheter was inserted into the pleural cavity under general anesthesia for injection of air or saline solution. A Vivid Q ultrasound with a 12L-RS linear probe was used. A baseline preintervention evaluation and 2 postintervention evaluations (one after theoretical class and the other after additional training with the animal model) were made. Sensitivity and specificity with the 95% confidence interval for recognition of the 3 patt...
Journal of the American Heart Association, 2014
Background--Small and large preclinical animal models have shown that antagomir-92a-based therapy... more Background--Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects.

Journal of pediatric orthopedics
Extremity amniotic band (EAB) syndrome can cause an intrauterine amputation as a result of a mech... more Extremity amniotic band (EAB) syndrome can cause an intrauterine amputation as a result of a mechanical effect with progressive strangulation. The aim of the study is to assess the use of fetal surgery of EABs with risk of amputation in the ovine fetus. Right limbs of fifteen 60-day-gestational age fetal sheep were ligated with silk suture at the infracondylar level. Left limbs were used for paired comparison. Fetuses were randomized into 3 groups: an early-repair group (n = 5), a late-repair group (n = 5), and a nonrepaired group (n = 5). The limbs of the 2 repaired groups underwent fetal release. The limbs obtained from at-term fetuses were analyzed morphologically, functionally, and radiologically. Statistical analysis with paired test was used to compare data. Nonrepaired limbs showed amputation or quasi amputation; the repaired ones did not. However, those late-repaired had significantly reduced passive ankle range of motion, shorter limb length, and mild residual changes. Intr...
Cirugía Española, 2009
informació n del artí culo Historia del artículo: Recibido el 26 de noviembre de 2008 Aceptado el... more informació n del artí culo Historia del artículo: Recibido el 26 de noviembre de 2008 Aceptado el 26 de noviembre de 2008 On-line el 18 de abril de 2009 Palabras clave: NOTES Cirugía endoscó pica transorificial Cirugía endoscó pica transgá strica Cirugía endoscó pica transvaginal Cirugía endoscó pica transesofá gica r e s u m e n Introducción: La aparició n de la cirugía endoscó pica transorificial (NOTES) y de nuevos prototipos para su realizació n nos llevó a diseñ ar un programa de cirugía experimental.

European Psychiatry, 2011
ABSTRACT Introduction The concept of unipolar mania has been raised, rejected and resurrected by ... more ABSTRACT Introduction The concept of unipolar mania has been raised, rejected and resurrected by a number of authors, and its true position within bipolar affective disorders is still a subject of debate. Clinical case A 52-year-old Caucasian woman was presented to the emergency room accompanied by family members because she had seven days without sleeping, exaggerated self-confidence and was engaged in multiple activities. Discussion At the mental examination she presented irritability, agitation, elation of mood, verbiage, sexual disinhibition, delusional activity of persecutory content, absence of insight. She had three manic episodes earlier and she didn’t have therapeutic adherence. The patient maintained an optimal level of performance functioning between maniac episodes, and also had no earlier depressive episodes. She described herself as a very creative, original, friendly, outgoing, sociable, responsible person. She had no family history of bipolar disease or other psychiatric disorder. An hemogram, basic biochemical investigations, cerebral TC, ilicits drugs screen and EEG were preformed showing no relevant alterations. She was admitted at an acute care psychiatric unit for 16 days. She had a good response to risperidone 2mg and 1000mg of divalproex sodium and to cognitive behavioural treatment. Conclusion Due to her previous 3 and her current manic episodes, without history of depressive symptoms, we concluded by the diagnosis of unipolar mania. Although there are certain sociodemographic and clinical variables that overlap, there does seem to be recent evidence concerning clinical, psychopathological and treatment features indicating a nosological separation of unipolar mania from bipolar mania.
European Psychiatry, 2011

European Psychiatry, 2010
ABSTRACT Introduction The impact of Idiopathic Parkinson Disease (IPD) in patient’s sexual health... more ABSTRACT Introduction The impact of Idiopathic Parkinson Disease (IPD) in patient’s sexual health is still a matter of debate. Clinicians should have a concern about the sexual function of their patients with IPD. Aims To evaluate sexual health of patients with IPD. Methods We randomly select a group of IPD patients and a group of healthy controls. We used the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) to assess sexual function. To evaluate depression and anxiety we used Brief Symptom Inventory (BSI) and Beck Depression Index (BDI). Results We had 83 IPD patients, and 69 controls. Male patients had lower total IIEF scores than controls (p&lt; 0,001). The analysis of linear regression shows a relationship between the IIFE and the duration of the disease, the patient age and the BDI score (R=0,72; Adjusted R square=0,49, p&lt; 0,001) when adjusted to the variables: realization of deep brain cirurgy of subthalamic nucleus (DBS-STN) stage of the disease, BSI score, dopaminergic treatment, treatment with antidepressives and antipsychotics. The IFSF didn’t show differences between the cases and the controls. Patients had higher BSI and BDI scores than controls (p&lt; 0,001). Conclusions Male IPD patients had an impairment of sexual function predicted by disease duration, patient age and BDI scores. Sexual function should be assessed in these patients
European Psychiatry, 2009

Cancer Research, 2009
Colorectal cancer is the second cause of cancer-related death in the western world, and although ... more Colorectal cancer is the second cause of cancer-related death in the western world, and although the genetic and molecular mechanisms involved in the initiation and progression of these tumors are among the best characterized, there are significant gaps in our understanding of this disease. The role of EPHB signaling in colorectal cancer has only recently been realized. Here, we use animal models to investigate the role of EphB4 in intestinal tumorigenesis. Modulation of EPHB4 levels in colon cancer cell lines resulted in significant differences in tumor growth in a xenograft model, with low levels of EPHB4 associated with faster growth. In addition, using a genetic model of intestinal tumorigenesis where adenomatous polyposis coli (Apc) mutations lead to initiation of the tumorigenic process (Apc(min) mice), we show that inactivation of a single allele of EphB4 results in higher proliferation in both the normal epithelium and intestinal tumors, significantly larger tumors in the small intestine, and a 10-fold increase in the number of tumors in the large intestine. This was associated with a 25% reduction in the lifespan of Apc(min) mice (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Gene expression analysis showed that EphB4 mutations result in a profound transcriptional reprogramming, affecting genes involved in cell proliferation, remodeling of the extracellular matrix, and cell attachment to the basement membrane among other functional groups of genes. Importantly, in agreement with the expression profiling experiments, using an in vitro assay, we show that loss of EPHB4 in colon cancer cells results in a significantly increased potential to invade through a complex extracellular matrix. Collectively, these results indicate that EphB4 has tumor suppressor activities and that regulation of cell proliferation, extracellular matrix remodeling, and invasive potential are important mechanisms of tumor suppression.

Lab animal, Jan 21, 2015
Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contri... more Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contribute to multimodal approaches to pain management in research animals. Ultrasound guidance is an emerging aspect of regional anesthesia that has the potential to optimize local delivery and distribution of anesthetic agents, thereby reducing the amounts of these agents that must be administered. The authors developed an ultrasound-guided technique for effective block of the axillary brachial plexus in rabbits. They used this technique to carry out nerve block in 14 rabbits. The procedure was accomplished in a relatively short amount of time and achieved successful nerve block in all rabbits with no adverse effects. Sonographic visualization of the distribution of the local anesthetic ropivacaine led to administration of smaller anesthetic doses in eight of the rabbits without affecting the duration of nerve block. The authors conclude that their technique is feasible and safe and provides...
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Papers by Marielle Esteves