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1.
Spine Surg Relat Res ; 7(3): 211-218, 2023 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-37309497

RESUMEN

Background: Thoracolumbar burst fractures (BFs) are traumatic lesions instigated by compression forces. Canal compression and compromise may lead to neurological deficits. Optimal surgical management is yet to be fully defined since various approaches such as anterior, posterior, or combined exist. This study aims to determine the operative performance of these three treatment modalities. Methods: In accordance with the PRISMA guidelines, a systematic review was performed, identifying studies comparing anterior, posterior, and/or combined surgical approaches in patients with thoracolumbar BFs. To analyze available evidence, a Bayesian network meta-analysis framework was utilized. Results: In this study, 16 studies were included. The shortest operative times and lowest operative blood losses were found for a posterior approach. The length of stay (LoS) was shorter with the posterior approach compared with the other two modalities. Return to work, postoperative kyphotic angle (PKA), and complications all favored the posterior approach. The visual analog scale score was similar between groups. Conclusions: This study suggests that the posterior approach has significant advantages in terms of operative time, blood loss, LoS, PKA, return to work, and complication rates when compared to the other approaches. Treatment should remain an individualized process, and before choosing an approach, factors such as patient characteristics, surgeon experience, and hospital settings should be considered.

2.
Turk J Surg ; 38(2): 121-133, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36483172

RESUMEN

Objectives: Orthotopic liver transplantation (OLT) remains the definitive treatment for patients afflicted with end-stage liver disease (ESLD). Transjugular intrahepatic portosystemic shunts (TIPS) have been adapted as a bridge to transplantation, allowing partial normalization of portal pressure and associated symptom improvement. Conflicting evidence exists on TIPS' impact on operative procedures. This study aimed to analyze available evidence on patients who underwent OLT with prior TIPS compared to OLT alone with the intent to determine TIPS' impact on surgical outcomes. Material and Methods: Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing TIPS + OLT versus OLT alone in patients with ESLD. Data were analyzed using Review Manager 5.3. Results: Thirteen studies were included. Operative time, packed red blood cells transfusions, intensive care unit admission, length of stay, dialysis, serum creatinine levels, ascites, vascular complications, bleeding revisions, reintervention, and other complications rates were similar between both groups. Fresh frozen plasma transfusion -2.88 units (-5.42, -0.35; p= 0.03), was lower in the TIPS + OLT group. Conclusion: Our study found TIPS can be safely employed without having detrimental impacts on OLT outcomes, furthermore, these findings also suggest TIPS does not increase bleeding or complications.

3.
Spine Surg Relat Res ; 6(2): 99-108, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35478987

RESUMEN

Background: A thoracolumbar burst fracture (BF) is a severe type of compression fracture, which is the most common type of traumatic spine fractures. Generally, surgery is the preferred treatment, but whether the optimal approach is either an anterior or a posterior approach remains unclear. This study aims to determine whether either method provides an advantage. Methods: Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing anterior versus posterior surgical approaches in patients with thoracolumbar BFs. Data were analyzed using Review Manager 5.3. Seven studies were included. Results: An operative time of 87.97 min (53.91, 122.03; p<0.0001) and blood loss of 497.04 mL (281.8, 712.28; p<0.0001) were lower in the posterior approach. Length of hospital stay, complications, reintervention rate, neurological outcomes, postoperative kyphotic angle, and costs were similar between both groups. Conclusions: Surgical intervention is usually selected to rehabilitate patients with BFs. The data obtained from this study suggest that a posterior approach represents a viable alternative to an anterior approach, with various advantages such as a shorter operative time and decreased bleeding.

4.
J Cardiovasc Surg (Torino) ; 63(3): 353-368, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35343660

RESUMEN

INTRODUCTION: Coronary artery bypass graft is the mainstay of treatment for multivessel coronary artery disease and is superior to percutaneous coronary intervention. Combined approaches such as hybrid coronary revascularization integrate coronary artery bypass grafting with percutaneous coronary intervention during the same procedure or weeks apart. These attempt to improve surgical morbidity and long-term outcomes. EVIDENCE ACQUISITION: Per PRISMA criteria, a systematic review of keywords "Hybrid Revascularization," "Hybrid Coronary Revascularization," "Surgical," "Surgery," "Treatment," "CABG," "HCR" and "PCI" was conducted in PubMed, EMBASE and SCOPUS. Studies comparing this technique's performance on either single or two-stage approach against traditional multiple vessel coronary artery bypass grafting were screened and analyzed for our review. EVIDENCE SYNTHESIS: Twenty-two studies totaling 6981 participants were ultimately included for analysis. Mean differences in operative time, bleeding, ventilator time and length of stay were significantly lower in the hybrid coronary revascularization group. Odds ratios in transfusions and in-hospital myocardial infarction were also lower in the hybrid coronary revascularization group. Results for in-hospital and all-cause mortality, major adverse cardiac events (MACE), stroke, reintervention, and complete revascularization were not significantly different. CONCLUSIONS: Our analysis shows hybrid coronary revascularization is a feasible alternative to traditional coronary artery bypass grafting. Short-and long-term outcomes including mortality, MACE, and postoperative morbidity are similar between both groups, while hybrid approaches are associated with decreased perioperative morbidity.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Resultado del Tratamiento
5.
Prostate ; 82(4): 405-414, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34985775

RESUMEN

CONTEXT: Prostate cancer is the most common cancer in men; robotic prostatectomy has cemented itself as part of the standard of care. Since its approval by the Food and Drug Administration in 2018, the SP console's application has been increasingly studied and compared with the multiport (MP) robotic approach. METHODS: Following PRISMA guidelines and PROSPERO registration CRD42021228744, a systematic review was performed in April 2021 on single-port robotic-assisted radical prostatectomies (SP-RARPs) compared to MP. Outcomes of interest were operative time, bleeding, complications, analgesic use, and postoperative continence, and erectile function. Data were analyzed with Review Manager 5.3. RESULTS: Seven studies were included, of which six studies met the inclusion criteria for quantitative synthesis, totalling 1068 patients, out of which 324 underwent SP-RARP and 744 underwent MP-RARP. No differences were found in baseline characteristics such as age, body mass index, prostatic-specific antigen, or stage. No differences in blood loss-15.77 mL [-42.44, 10.89], p = 0.25, operative time 3.93 min [-4.12, 11.98], p = 0.34, or positive surgical margins, with an odds ratio (OR) of 0.78 [0.55, 1.10], p = 0.15-were found. Length of stay was significantly shorter in SP -0.94 days [-1.56, -0.33], p = 0.003, with no differences in complication rates, with an OR of 1.29 [0.78, 2.14], p = 0.32, continence rates, with an OR of 1.29 [0.90, 1.83], p = 0.16, erectile function, with an OR of 0.86 [0.52, 1.40], p = 0.54, or biochemical recurrence. Qualitative evidence suggests decreased opioid consumption. CONCLUSION: SP-RARPs are feasible alternatives to the traditional MP with possible benefits in pain management and length of stay. Future high-quality studies are needed to confirm these findings.


Asunto(s)
Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Pérdida de Sangre Quirúrgica , Humanos , Tiempo de Internación , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Resultado del Tratamiento
6.
Asian Spine J ; 16(4): 583-597, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34465015

RESUMEN

Bones are the third most common location for solid tumor metastasis affecting up to 10% of patients with solid tumors. When the spine is involved, thoracic and lumbar vertebrae are frequently affected. Access to spinal lesions can be through minimally invasive surgery (MIS) or traditional open surgery (OS). This study aims to determine which method provides an advantage. Following the PRISMA (Preferred Inventory for Systematic Reviews and Meta-Analysis) guidelines, a systematic review was conducted to identify studies that compare MIS with OS in patients with spinal metastatic disease. Data were analyzed using Review Manager ver. 5.3 (RevMan; Cochrane, London, UK). Ten studies were included. Operative time was similar among groups at -35.23 minutes (95% confidence interval [CI], -73.36 to 2.91 minutes; p=0.07). Intraoperative bleeding was lower in MIS at -562.59 mL (95% CI, -776.97 to -348.20 mL; p<0.00001). OS procedures had higher odds of requiring blood transfusions at 0.26 (95% CI, 0.15 to 0.45; p<0.00001). Both approaches instrumented similar numbers of levels at -0.05 levels (95% CI, -0.75 to 0.66 levels; p=0.89). We observed a decreased need for postoperative bed rest at -1.60 days (95% CI, -2.46 to -0.74 days; p=0.0003), a shorter length of stay at -3.08 days (95% CI, -4.50 to -1.66 days; p=0.001), and decreased odds of complications at 0.60 (95% CI, 0.37 to 0.96; p=0.03) in the MIS group. Both approaches revealed similar reintervention rates at 0.65 (95% CI, 0.15 to 2.84; p=0.57), effective rates of reducing metastasis-related pain at -0.74 (95% CI, -2.41 to 0.94; p=0.39), and comparable scores of the Tokuhashi scale at -0.52 (95% CI, -2.08 to 1.05; p=0.41), Frankel scale at 1.00 (95% CI, 0.60 to 1.68; p=1.0), and American Spinal Injury Association Scale at 0.53 (95% CI, 0.21 to 1.37; p=0.19). MIS appears to provide advantages over OS. Larger and prospective studies should fully detail the role of MIS as a treatment for spine metastasis.

9.
Pediatr Surg Int ; 37(11): 1477-1487, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34269866

RESUMEN

Hepatoportoenterostomy remains the cornerstone of treatment for biliary atresia. Current employed techniques include laparoscopy and open surgery. This study aims to determine if either method provides an advantage. Following PRISMA guidelines, a systematic review was conducted. Nineteen studies were included. Mean operative time 34.98 (95% CI 20.10, 49.85; p ≤ 0.00001) was longer in laparoscopic while bleeding volumes - 16.63 (95% CI - 23.39, - 9.86; p ≤ 0.00001) as well as the time to normal diet - 2.42 (95% CI - 4.51, - 0.32; p = 0.02) were lower in the laparoscopic group. No differences were observed in mean length of stay - 0.83. Similar complication, transfusions, postoperative cholangitis 0.97, and transplant free survival rates 1.00 (0.63, 1.60; p = 0.99) were seen between groups. Laparoscopic portoenterostomy provides advantages on operative time and bleeding as well as to normal diet when compared to open procedures. Both procedures showed no differences in length of stay, complications, cholangitis, and importantly, native liver survival. Level of evidence: III.


Asunto(s)
Atresia Biliar , Laparoscopía , Atresia Biliar/cirugía , Humanos , Lactante , Tempo Operativo , Portoenterostomía Hepática , Resultado del Tratamiento
10.
Pediatr Surg Int ; 37(10): 1313-1322, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34115175

RESUMEN

Choledochal cysts are a rare pediatric biliary pathology. Excision of the extrahepatic cyst and restoration of biliary-enteric continuity through either hepaticoduodenostomy (HD) or Roux-en-Y hepaticojejunostomy (HJ) is the mainstay treatment. This study aims to determine if either method provides an advantage. Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing hepaticojejunostomy to hepaticoduodenostomy in patients with choledochal cysts. Data were analyzed using Review Manager 5.3. Nine studies were included, operative time was shorter - 97.50 [- 172.31, - 22.69] p = 0.01 and bleeding reduced - 48.98 [- 88.25, - 9.71] p = 0.01 in HD. HD was associated with shorter length of stay 2.18 [- 3.87, - 0.50] p = 0.01 and similar cholangitis and reintervention rates. Time to a normal diet was similar between groups. Biliary reflux was seen more frequently in HD 19.14 [2.60, 140.63] p = 0.004. Complications such as leak and cholangitis were similar between groups. HD represents a viable alternative to HJ with various advantages such as shorter operative time, decreased bleeding and shorter length of hospital stay. Bile reflux remains a major limitation.Level of evidence IV.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Biliar , Quiste del Colédoco , Anastomosis en-Y de Roux , Anastomosis Quirúrgica , Niño , Quiste del Colédoco/cirugía , Humanos , Estudios Retrospectivos
11.
Cardiovasc Res ; 113(2): 207-221, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28025386

RESUMEN

AIM: To analyse the ability of TWEAK to modify the endothelin system, particularly endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1), studying the intracellular mechanisms implied. TNF-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily; it has different biological functions such as inflammation, angiogenesis, proliferation, and apoptosis. TWEAK and fibroblast growth-factor-inducible 14 are expressed in different cell types, including endothelial and smooth muscle cells. Despite their presence in endothelial cells, the effect of TWEAK on endothelial function is incompletely defined. METHODS AND RESULTS: In cells, TWEAK induced protein (Western blot) and mRNA (quantitative polymerase chain reaction) expression of ECE-1. Results were related to transcriptional changes, as ECE-1 promoter activity (transfection assays) was also increased. Transfections with serial deletions of ECE-1 promoter suggest a potential role for AP-1 and NFkB, which were confirmed by electrophoretic mobility shift assays. When AP-1 or NFkB activations were inhibited by specific inhibitors of AP-1, PD-98059 (Erk1/2 inhibitor), or SP-600125 (JNK inhibitor), and also with an inhibitor of NFKB and PDTC, TWEAK effect was partially blocked in both cases, suggesting that both transcription factors are implied in ECE-1 regulation. Moreover, the endothelial changes induced by TWEAK were also tested in vivo, using 3-month-old male CD-1 mice treated with TWEAK 10 µg/kg body weight for 24 h, finding similar effects, a rise in ET-1 production (enzyme-linked immunosorbent assay), and ECE-1 expression in aorta and lung tissues. Mice showed slight hypertension after 4 h of treatment, which disappeared at 24 h. CONCLUSIONS: In pathological situations such as chronic inflammation, TWEAK could be more harmful through this effect at endothelial level. Pharmacological blockade of this cytokine could prevent the haemodynamic and structural changes related to an increased ET-1 synthesis.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Endotelina-1/metabolismo , Enzimas Convertidoras de Endotelina/metabolismo , Factores de Necrosis Tumoral/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Línea Celular , Células Endoteliales/enzimología , Endotelina-1/genética , Enzimas Convertidoras de Endotelina/genética , Humanos , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/fisiopatología , Técnicas In Vitro , Masculino , Ratones , FN-kappa B/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo , Factor de Transcripción AP-1/metabolismo , Transcripción Genética , Transfección , Factores de Necrosis Tumoral/toxicidad , Regulación hacia Arriba
12.
Am J Physiol Endocrinol Metab ; 307(12): E1085-96, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25336523

RESUMEN

Despite the presence of vitamin D receptor (VDR) in endothelial cells, the effect of vitamin D on endothelial function is unknown. An unbalanced production of vasoactive endothelial factors such as nitric oxide (NO) or endothelin-1 (ET-1) results in endothelial dysfunction, which can alter the normal cardiovascular function. Present experiments were devoted to assess the effect of active vitamin D (calcitriol) on the synthesis of endothelial vasoactive factors. The results were that, in cells, calcitriol increased ET-1 and NO productions, which were measured by ELISA and fluorimetric assay, respectively. Calcitriol also increased endothelin-converting enzyme-1 (ECE-1) and endothelial-nitric oxide synthase (eNOS) activities, their mRNA (qPCR), their protein expressions (Western-blot), and their promoter activities (transfection assays). Calcitriol did not change prepro-ET-1 mRNA. The effect was specific to VDR activation because when VDR was silenced by siRNA, the observed effects disappeared. Mechanisms involved in each upregulation differed. ECE-1 upregulation depended on AP-1 activation, whereas eNOS upregulation depended directly on VDR activation. To evaluate the in vivo consequences of acute calcitriol treatment, normal Wistar rats were treated with a single ip injection of 400 ng/kg calcitriol and euthanized 24 h later. Results confirmed those observed in cells, that production and expression of both factors were increased by calcitriol. Besides, calcitriol-treated rats showed a slight rise in mean blood pressure, which decreased when pretreated with FR-901533, an ECE-1 antagonist. We conclude that calcitriol increases the synthesis of both ET-1 and NO in endothelial cells. However, the ET-1 upregulation seems to be biologically more relevant, as animals acutely treated with calcitriol show slight increases in blood pressure.


Asunto(s)
Calcitriol/farmacología , Células Endoteliales/efectos de los fármacos , Endotelinas/metabolismo , Óxido Nítrico/metabolismo , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/fisiología , Enzimas Convertidoras de Endotelina , Humanos , Masculino , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas Wistar , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
13.
Pharmacol Res ; 76: 106-18, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23911580

RESUMEN

Although calcimimetics were developed to block parathyroid hormone synthesis, some reports suggest that they may also reduce blood pressure by unknown mechanisms. Calcimimetic-induced changes in the synthesis of endothelial vasoactive factors could be involved. Wistar rats were treated with the calcimimetic R-568, and systolic blood pressure (SBP) was registered with a tail-cuff sphygmomanometer, the content of endothelial nitric oxide synthase (eNOS) and endothelin-converting enzyme (ECE-1) in tissue was evaluated by immunohistochemistry and Western blot, circulating levels of endothelin-1 (ET-1) were measured by ELISA. R-568 reduced SBP and circulating levels of ET-1, without changes in eNOS expression. In contrast, R-568 increased the lung and vascular content of ECE-1. In order to analyze the mechanisms involved, we studied the effect of R-568 on human endothelial cells. R-568 did not modify neither eNOS protein content nor pre-pro-ET-1 mRNA expression, but increased ECE-1 protein content, and decreased ET-1 synthesis and ECE-1 activity. The inhibition of ECE-1 activity was very strong, similar to the classic ECE inhibitor phosphoramidon, the addition of exogenous zinc restored enzymatic activity. Moreover, the amount of zinc in immunoprecipitated ECE from R-568 treated cells was 3-fold less than in control cells. In conclusion, R-568 inhibits ECE by expelling zinc from the enzyme, with the subsequent decrease in enzymatic activity and reducing circulating levels of ET-1, which may be responsible for the lower SBP observed in R-568-treated rats. This descent would be partially compensated by the increased synthesis of the ECE-1 itself, and by other homeostatic mechanisms that regulate SBP.


Asunto(s)
Compuestos de Anilina/farmacología , Ácido Aspártico Endopeptidasas/metabolismo , Calcio/agonistas , Metaloendopeptidasas/metabolismo , Animales , Ácido Aspártico Endopeptidasas/análisis , Presión Sanguínea/efectos de los fármacos , Línea Celular , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelina-1/sangre , Endotelina-1/metabolismo , Enzimas Convertidoras de Endotelina , Humanos , Masculino , Metaloendopeptidasas/análisis , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/análisis , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fenetilaminas , Propilaminas , Ratas , Ratas Wistar
14.
Arterioscler Thromb Vasc Biol ; 31(11): 2577-85, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21852564

RESUMEN

OBJECTIVE: Endothelial function depends on the equilibrium in the synthesis of vasoactive endothelial factors. It is well known that endothelin and nitric oxide (NO) exhibit reciprocal regulation. We assessed the ability of NO to regulate endothelin-converting enzyme-1 (ECE-1) expression in vascular endothelial cells. METHODS AND RESULTS: Bovine aortic endothelial cells were incubated with 2 different NO donors as well as with a cyclic-GMP analog, dibutyryl-cGMP (dB-cGMP). ECE-1 protein content and mRNA expression were evaluated by Western blot and Northern blot, respectively, promoter activity by transfection experiments, ECE-1 activity by ELISA, and cGMP production by radioimmunoassay. Both NO donors decreased ECE-1 protein content, mRNA expression, and ECE-1 activity. ODQ, an inhibitor of soluble guanylyl cyclase, blocked those effects. NO donors raised cGMP levels, and dB-cGMP mimicked their effects on ECE-1 expression, which were blocked by KT5823, a nonspecific PKG inhibitor. The changes on ECE-1 expression were due to a destabilization on 3'-untranslated region (3'-UTR) of this mRNA, because the activity of a luciferase reporter construct containing the 3'-UTR of the ECE-1 gene was reduced by dB-cGMP in a PKG-dependent manner. The biological relevance of this regulation was confirmed in bovine aortic endothelial cells coincubated with macrophages in the presence of lipopolysaccharide, in eNOS-deficient mice, and in Wistar rats treated with NO donors. In every case, an inverse relationship was observed between NO and ECE-1 protein content. CONCLUSION: Our results support that NO regulates ECE-1 expression through a cGMP/PKG-dependent regulatory mechanism at the post-transcriptional level via the 3'-UTR of the ECE-1 gene.


Asunto(s)
Ácido Aspártico Endopeptidasas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Metaloendopeptidasas/metabolismo , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico/metabolismo , ARN Mensajero/metabolismo , Animales , Aorta/citología , Aorta/efectos de los fármacos , Aorta/metabolismo , Ácido Aspártico Endopeptidasas/genética , Bovinos , Línea Celular , Técnicas de Cocultivo , GMP Cíclico/metabolismo , GMP Cíclico/farmacología , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Regulación hacia Abajo/fisiología , Enzimas Convertidoras de Endotelina , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Guanilato Ciclasa/metabolismo , Células HEK293 , Humanos , Riñón/citología , Riñón/efectos de los fármacos , Riñón/embriología , Riñón/metabolismo , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloendopeptidasas/genética , Ratones , Ratones Noqueados , Modelos Animales , Óxido Nítrico Sintasa de Tipo III/deficiencia , Óxido Nítrico Sintasa de Tipo III/genética , ARN Mensajero/efectos de los fármacos , Ratas Wistar
15.
Hum Mol Genet ; 18(10): 1795-804, 2009 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-19246517

RESUMEN

Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.


Asunto(s)
Trastorno Autístico/genética , Trastorno Autístico/metabolismo , Dosificación de Gen , Fosfatidilinositoles/metabolismo , Transducción de Señal , Sinapsis/metabolismo , Trastorno Autístico/etiología , Hibridación Genómica Comparativa , Humanos , Masculino , Sinapsis/genética
16.
Arch Esp Urol ; 61(7): 786-92, 2008 Sep.
Artículo en Español | MEDLINE | ID: mdl-18972913

RESUMEN

OBJECTIVES: Proper treatment of neurogenic hyperactive detrusor muscle is responsible for several features essential for life such as renal function, and quality of life relevant issues such as urinary incontinence. Anticholinergic drugs allow treatment in most cases, but their failure in cases of refractory neurogenic hyperactive detrusor is a challenge. To evaluate the efficacy of detrusor injection of type A botulin toxin in patients with refractory neurogenic hyperactive detrusor, on the following urodynamic parameters: maximum cystomanometric capacity, detrusor compliance, reflex volume, maximum detrusor pressure and post void residual. METHODS: Prospective study in 16 patients with the diagnosis of neurogenic hyperactive detrusor refractory to anticholinergic therapy. Urodynamic studies were performed 30 and 60 days before the procedure and after at least two weeks from stopping anticholinergic therapy. 300 units of type A botulin toxin (BTX-A) were endoscopically injected in 30 punction sites, 10 units per ml each punction. Urodynamic control was performed 30 to 45 days after injection. RESULTS: Six of the 16 patients in the study where females and 11 males; mean age was 39.5 years (22 to 63 years). Urodynamic results: mean maximum capacity on cystomanometry before BTXA was 204.73 ml and after BTX-A 381.87 ml. Maximum detrusor capacity before was 91.46 H2O cm whereas post-treatment was 41.2 H2O cm. Mean final filling pressure was 68 H2O cm before treatment and 34 H2O cm after. Mean reflex volume was 111.33 ml before and 310.8 ml after. Finally, mean post void residual before BTX-A was 129.6 ml whereas post-BTX-A was 345.9 ml. CONCLUSIONS: The injection of 300 U of type A botulin toxin in the detrusor muscle has demonstrated to be effective and safe for the treatment of refractory neurogenic hyperactive detrusor. There were statistically significant differences in the urodynamic parameters before and after the injection. There were no significant adverse events.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Neurotoxinas/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/fisiopatología , Urodinámica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso/fisiopatología , Estudios Prospectivos , Adulto Joven
17.
Arch. esp. urol. (Ed. impr.) ; 61(7): 786-792, sept. 2008. tab
Artículo en Es | IBECS | ID: ibc-67736

RESUMEN

Objetivos: Del correcto tratamiento del detrusor hiperactivo neurogénico dependen aspectos fundamentales para la vida como la suficiencia renal hasta aspectos de importancia relevante para la calidad de vida como la incontinencia urinaria. Los fármacos anticolinérgicos permiten el tratamiento en la mayoría de los casos, pero su fracaso en el detrusor hiperactivo neurogénico refractario constituye un desafío. Evaluar de la eficacia de la inyección intradetrusorial de toxina botulínica tipo A en pacientes con detrusor hiperactivo neurogénico refractario, en los siguientes parámetros urodinámicos: capacidad cistomanométrica máxima, acomodación del detrusor, volumen de reflejo, presión máxima del detrusor y residuo postmiccional. Métodos: Estudio prospectivo en 16 pacientes con diagnóstico de detrusor hiperactivo neurogénico refractario a la terapia anticolinérgica. Se realizó investigación urodinámica 30 a 60 días previos al procedimiento y luego de la interrupción de por lo menos 2 semanas de la terapia anticolinérgica. Se realizó la inyección endoscópica de 300 U de Toxina Botulínica tipo A (BTX-A) en 30 sitios de punción, a 10 unidades por ml por punción. Se realizó el control urodinámico 30 a 45 días posteriores a la inyección. Resultados: De los 16 pacientes estudiados 5 eran mujeres y 11 hombres, la edad media fue de 39,5 años (22 a 63 años). Los resultados urodinámicos hallados fueron: Capacidad cistomanométrica máxima media pre BTX-A fue de 204.73 ml y la posterior fue de 381.87 ml. La presión máxima del detrusor media previa fue de 91.46 cm H2O mientras que la posterior fue 41.2 cm H2O. La presión de fin de llenado media previa fue de 68 cm H2O y la posterior 34 cm H2O. El volumen reflejo medio previo fue de 111.33 ml, mientras que el posterior fue de 310.8 ml. Por último el residuo postmiccional pre-BTX-A medio fue de 129.6 ml mientras que el post-BTX-A de 345.9 ml. Conclusiones: La inyección de 300 U de toxina botulínica tipo A en el detrusor ha demostrado ser eficaz y segura para el tratamiento del detrusor hiperactivo neurogénico refractario. En los parámetros urodinámicos se observaron diferencias estadísticamente significativas antes y después de la inyección. No se presentaron efectos adversos significativos (AU)


Objectives: Proper treatment of neurogenic hyperactive detrusor muscle is responsible for several features essential for life such as renal function, and quality of life relevant issues such as urinary incontinence. Anticholinergic drugs allow treatment in most cases, but their failure in cases of refractory neurogenic hyperactive detrusor is a challenge. To evaluate the efficacy of detrusor injection of type A botulin toxin in patients with refractory neurogenic hyperactive detrusor, on the following urodynamic parameters: maximum cystomanometric capacity, detrusor compliance, reflex volume, maximum detrusor pressure and post void residual. Methods: Prospective study in 16 patients with the diagnosis of neurogenic hyperactive detrusor refractory to anticholinergic therapy. Urodynamic studies were performed 30 and 60 days before the procedure and after at least two weeks from stopping anticholinergic therapy. 300 units of type A botulin toxin (BTX-A) were endoscopically injected in 30 punction sites, 10 units per ml each punction. Urodynamic control was performed 30 to 45 days after injection. Results: Six of the 16 patients in the study where females and 11 males; mean age was 39.5 years (22 to 63 years). Urodynamic results: mean maximum capacity on cystomanometry before BTX A was 204.73 ml and after BTX-A 381.87 ml. Maximum detrusor capacity before was 91.46 H2O cm whereas post-treatment was 41.2 H2O cm. Mean final filling pressure was 68 H2O cm before treatment and 34 H2O cm after. Mean reflex volume was 111.33 ml before and 310.8 ml after. Finally, mean post void residual before BTX-A was 129.6 ml whereas post-BTX-A was 345.9 ml. Conclusions: The injection of 300 U of type A botulin toxin in the detrusor muscle has demonstrated to be effective and safe for the treatment of refractory neurogenic hyperactive detrusor. There were statistically significant differences in the urodynamic parameters before and after the injection. There were no significant adverse events (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Urodinámica , Estudios Prospectivos , Resultado del Tratamiento
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