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1.
Front Surg ; 10: 1095224, 2023.
Article in English | MEDLINE | ID: mdl-37215356

ABSTRACT

Objectives: The study aimed to identify differences and compare anatomical and biomechanical features between elective and ruptured abdominal aortic aneurysms (AAAs). Methods: Data (clinical, anatomical, and biomechanical) of 98 patients with AAA, 75 (76.53%) asymptomatic (Group aAAA) and 23 (23.46%) ruptured AAA (Group rAAA), were prospectively collected and analyzed. Anatomical, morphological, and biomechanical imaging markers like peak wall stress (PWS) and rupture risk equivalent diameter (RRED), comorbid conditions, and demographics were compared between the groups. Biomechanical features were assessed by analysis of Digital Imaging and Communication in Medicine images by A4clinics (Vascops), and anatomical features were assessed by 3Surgery (Trimensio). Binary and multiple logistic regression analysis were used and adjusted for confounders. Accuracy was assessed using receiving operative characteristic (ROC) curve analysis. Results: In a multivariable model, including gender and age as confounder variables, maximal aneurysm diameter [MAD, odds ratio (OR) = 1.063], relative intraluminal thrombus (rILT, OR = 1.039), and total aneurysm volume (TAV, OR = 1.006) continued to be significant predictors of AAA rupture with PWS (OR = 1.010) and RRED (OR = 1.031). Area under the ROC curve values and correct classification (cc) for the same parameters and the model that combines MAD, TAV, and rILT were measured: MAD (0.790, cc = 75%), PWS (0.713, cc = 73%), RRED (0.717, cc = 55%), TAV (0.756, cc = 79%), rILT (0.656, cc = 60%), and MAD + TAV + rILT (0.797, cc = 82%). Conclusion: Based on our results, in addition to MAD, other important predictors of rupture that might be used during aneurysm surveillance are TAV and rILT. Biomechanical parameters (PWS, RRED) as valuable predictors should be assessed in prospective clinical trials. Similar studies on AAA smaller than 55 mm in diameter, even difficult to organize, would be of even greater clinical value.

2.
Angiol Sosud Khir ; 23(2): 159-163, 2017.
Article in English, Russian | MEDLINE | ID: mdl-28594810
3.
Eur J Vasc Endovasc Surg ; 51(6): 783-9, 2016 06.
Article in English | MEDLINE | ID: mdl-26860256

ABSTRACT

OBJECTIVE: The objective was to quantify aorto-iliac morphology differences between AAA patients of Caucasian and Asian origin. Additionally, the impact of patient demographic characteristics was assessed, which could influence the morphological differences. METHODS: This international multicentre study included two tertiary referral institutions from Europe and one from China. CT scans with 3D reconstruction of 296 patients with infrarenal AAA >5 cm were analysed. Eighteen measurements were recorded from each CT scan and compared between Caucasian and Asian patients. RESULTS: Caucasian patients had longer common iliac arteries (right: 65.0 vs. 33.1 mm, p < .001 left: 65.0 vs. 35.2 mm, p < .001), longer aneurysm neck (33.0 vs. 28.4 mm, p < .001), greater aneurysm to aortic axis angle (153.0° vs. 142.2°, p < .001), and longer combined aorto-iliac length (195.7 vs. 189.2 mm, p < .001). However, Asian patients had a longer infrarenal abdominal aorta (152.0 vs. 130.0 mm, p < .001), longer AAA (126.2 vs. 93.0 mm), and greater linear distance from renal artery to aorto-iliac bifurcation (143.6 vs. 116.0 mm, p < .001). Caucasian patients had a larger inner common iliac artery diameter (right: 16.0 vs. 14.9 mm, p < .001, left: 16.0 vs. 15.2 mm, p < .001), larger inner exernal iliac artery diameter (right: 9.0 vs. 7.5 mm, p < .001 left: 9.0 vs. 7.7 mm, p < .001), and larger inner common femoral artery diameter (right: 10.0 vs. 5.9 mm, p < .001 left: 10.0 vs. 6.1 mm, p < .001). No difference was observed in AAA transverse diameter (62.0 vs. 63.1 mm, p = .492). CONCLUSION: The results showed that aorto-iliac anatomy in Caucasians differs significantly from Asians, particularly in the length of the common iliac arteries and infrarenal abdominal aorta, and in the transverse diameter of the common, external iliac, and common femoral arteries. Therefore, the exact criteria for stent graft design are dependent on the racial origin of the patient.


Subject(s)
Aortic Aneurysm, Abdominal/pathology , Iliac Artery/anatomy & histology , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/surgery , Aortography/methods , Asian People , Blood Vessel Prosthesis Implantation/methods , Female , Humans , Iliac Artery/surgery , Male , Middle Aged , Renal Artery/surgery , Risk Factors , Treatment Outcome , White People
4.
J Cardiovasc Surg (Torino) ; 56(5): 737-44, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25868970

ABSTRACT

Spinal cord ischemia remains the most impressive and colliding complication following open surgical and endovascular aortic procedures. Paraparesis and paraplegia are devastating, having a major invalidating impact on the patient's life. Also for the surgeon and the entire team this dramatic adverse event causes a significant concussion. Surgeons faced this problem in practice in the 1950s when this surgery started being applied. Even A. Carrel in 1910 said, "The main danger of the aortic operation does not come from the heart or from the aorta itself, but from the central nervous system". As the number of these surgeries grew, some were followed by the spinal cord ischemia. Now, in 21st century, problem of spinal cord ischemia still exists. By understanding the reasons of its development we shall be able to find more useful methods for prevention as well as for the treatment. The aim of this article was to search what is behind this dreadful complication, explaining different mechanisms which take part in its development during endovascular and open surgical treatment.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Spinal Cord Ischemia/etiology , Aorta, Thoracic/physiopathology , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/physiopathology , Humans , Paraparesis/etiology , Paraplegia/etiology , Risk Factors , Spinal Cord Ischemia/diagnosis , Spinal Cord Ischemia/therapy , Treatment Outcome
6.
J Cardiovasc Surg (Torino) ; 56(3): 441-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24714682

ABSTRACT

AIM: He aim of this paper was to investigate the incidence of and the indications for conversion to general anesthesia (GA) in a large single-center series of patients undergoing carotid surgery under cervical plexus block (CPB). METHODS: With IRB approval we retrospectively analyzed the medical records of all patients who underwent carotid surgery under CPB from November 2007 to October 2010. Cervical plexus was blocked at both the superficial and deep levels. An intraluminal shunt was inserted in patients who demonstrated signs of inadequate cerebral perfusion upon carotid clamping (CC). Propofol was given to patients reporting pain or discomfort throughout the procedure. The primary outcomes were the number and percentage of conversions to GA as well as the indications for this intervention. The secondary outcome was the incidence of partial cervical block failure, defined as the need for supplemental propofol administration for pain relief during surgery. RESULTS: In total, 1464 carotid surgical procedures were performed under CPB in 1305 consecutive patients during the investigated period. Conversion to GA was required in 17 (1.2%) patients. The most common reason for conversion to GA was persisting neurological deterioration upon CC and intraluminal shunt insertion, which was recorded in 8/17 (47.1%) procedures. Other indications to convert were systemic toxicity of local anesthetics, pain, general discomfort and restlessness during surgery, and acute myocardial infarction. CONCLUSION: Cervical plexus block for carotid surgery is associated with a low rate of conversions to GA. Neurological deterioration upon carotid clamping and local anesthetic toxicity are identified as the most common indications for such intervention.


Subject(s)
Anesthesia, General , Anesthetics, Intravenous/administration & dosage , Anesthetics, Local/administration & dosage , Carotid Arteries/surgery , Cervical Plexus Block , Propofol/administration & dosage , Vascular Surgical Procedures , Aged , Anesthetics, Local/adverse effects , Carotid Arteries/physiopathology , Cervical Plexus Block/adverse effects , Constriction , Female , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Pain/etiology , Pain/prevention & control , Retrospective Studies , Seizures/chemically induced , Serbia , Treatment Failure , Unconsciousness/chemically induced , Vascular Surgical Procedures/adverse effects
7.
Rozhl Chir ; 93(7): 357-65, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25263471

ABSTRACT

Rupture is the most serious and lethal complication of the abdominal aortic aneurysm. Despite all improvements during the past 50 years, ruptured abdominal aortic aneurysms are still associated with very high mortality. Namely, including patients who die before reaching the hospital, the mortality rate due to abdominal aortic aneurysm rupture is 90%. On the other hand, during the last twenty years, the number of abdominal aortic aneurysms significantly increased. One of the reasons is the fact that in majority of countries the general population is older nowadays. Due to this, the number of degenerative AAA is increasing. This is also the case for patients with abdominal aortic aneurysm rupture. Age must not be the reason of a treatment refusal. Optimal therapeutic option ought to be found. The following article is based on literature analysis including current guidelines but also on my Clinics significant experience. Furthermore, this article show cases options for vascular medicine in undeveloped countries that can not apply endovascular procedures at a sufficient level and to a sufficient extent. At this moment the following is evident. Thirty-day-mortality after repair of ruptured abdominal aortic aneurysms is significantly lower in high-volume hospitals. Due to different reasons all ruptured abdominal aortic aneurysms are not suitable for EVAR. Open repair of ruptured abdominal aortic aneurysm should be performed by experienced open vascular surgeons. This could also be said for the treatment of endovascular complications that require open surgical conversion. There is no ideal procedure for the treatment of AAA. Each has its own advantages and disadvantages, its own limits and complications, as well as indications and contraindications. Future reductions in mortality of ruptured abdominal aortic aneurysms will depend on implementation of population-based screening; on strategies to prevent postoperative organ injury and also on new medical technology improvements. Taking this into consideration, education of young vascular surgeons in endovascular but also in open aortic surgery, is of vast importance.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Abdominal/physiopathology , Aortic Rupture/etiology , Aortic Rupture/mortality , Endovascular Procedures , Female , Humans , Length of Stay , Male , Postoperative Complications , Risk Factors , Treatment Outcome , Vascular Surgical Procedures/methods
8.
J Cardiovasc Surg (Torino) ; 55(6): 741-57, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25017787

ABSTRACT

This article discusses the etiology of spinal cord ischemia (SCI) mechanisms that may lead to paraplegia during open and endovascular repair from an anatomical and physiological perspective as well as the role of various protective measures used in prevention of this dreadful complication of aortic surgery. There are many adjuncts that must be considered to reduce the risk of spinal cord injury, such as revascularisation of intercostal arteries, maintenance of high mean blood pressure, spinal cord drainage and a few new promising models like NIRS and MISACE which usefulness is yet to be determined. These measures and techniques as well as possible etiology mechanisms of SCI are discussed, highlighting the evidence available for each method, the practical ways in which they may be used, giving some new theories and explanations.


Subject(s)
Aorta/surgery , Endovascular Procedures/adverse effects , Spinal Cord Ischemia/etiology , Spinal Cord/blood supply , Vascular Surgical Procedures/adverse effects , Aorta/physiopathology , Collateral Circulation , Hemodynamics , Humans , Paraplegia/etiology , Regional Blood Flow , Risk Factors , Spinal Cord Ischemia/physiopathology , Spinal Cord Ischemia/prevention & control , Treatment Outcome
10.
Vascular ; 22(5): 361-3, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24003007

ABSTRACT

Aneurysm of the persistent sciatic artery is a rare cause of limb ischemia, which is a challenge for both diagnosis and treatment. After successful diagnosis adequate treatment may require skills in open and endovascular surgery. We present a patient with the aneurysm of the persistent sciatic artery treated by bypass procedure with PTFE graft using posterior approach. We named this procedure "dorsal bypass". Detailed explanation of clinical presentation, diagnosis and the surgical procedure is given in this paper.


Subject(s)
Aneurysm/surgery , Arteries/abnormalities , Arteries/surgery , Leg/blood supply , Vascular Surgical Procedures/methods , Aged, 80 and over , Female , Humans
12.
Int Angiol ; 30(5): 434-40, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21873974

ABSTRACT

AIM: The aim of this paper was to determine the role of ultrasonographic examination in acute progressive thrombophlebitis (APT) of great saphenous vein (GSV) and its impact in considering indications for urgent surgical treatment. MEHODS: In this retrospective study, out of 141 consecutive patients operated due to APT of GSV above the knee, 63 were examined by ultrasonography prior surgery. RESULTS: Out of 63 operated patients, in 38 duplex ultrasonography (DUS) revealed that proximal level of phlebitic process was more than 5 cm higher than the one found during physical examination (60.3%). In this group, the mean difference between DUS and clinical finding was 8.5±3.5 cm. In 25 patients there were no differences greater than 5 cm found between DUS and physical examination (39.7%). There was statistically highly significant difference between DUS and physical examination findings (χ2=6.5, P<0.01). CONCLUSION: This study revealed significant difference between ultrasonographic and physical findings in patients with APT of GSV. DUS presented as reliable diagnostic method in examining, course-following and making decision for operative treatment of these patients.


Subject(s)
Saphenous Vein/diagnostic imaging , Saphenous Vein/surgery , Thrombophlebitis/diagnostic imaging , Thrombophlebitis/surgery , Ultrasonography, Doppler, Color , Vascular Surgical Procedures , Acute Disease , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Disease Progression , Female , Humans , Male , Middle Aged , Physical Examination , Predictive Value of Tests , Retrospective Studies , Serbia , Treatment Outcome
13.
Int Angiol ; 30(6): 534-40, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22233614

ABSTRACT

AIM: Horseshoe kidney is the most common congenital kidney anomaly, occurring in 0.15-0.25% of all newborns. A medial fusion of the kidneys, mostly anteriorly to the aorta, is the main characteristic of this anomaly. The co-existence of abdominal aortic aneurysm (AAA) and horseshoe kidney is rare, occurring only in 0.12% of patients. The aim of this paper is to define the optimal management of patients with AAA associated with the horseshoe kidney. METHODS: This paper presents the analysis of patients operated at the Clinic for Vascular and Endovascular Surgery of the Clinical Center of Serbia in Belgrade due to AAA associated with the horseshoe kidney as well as the analysis of the previously published literature data regarding this topic. RESULTS: Between 1985 and 2011, data were collected retrospectively on 25 patients with the horseshoe kidney who underwent aortic surgery. Out of them, 6 patients had aortoiliac occlusive disease and 19 patients had aortic aneurysm. More detailed analysis of the aneurysmatic group was performed. Among them there were 16 male and three female patients, with the average age of 63.8 (50-76) years. Two patients had type IV of thoracoabdomial aortic aneurysm (TAA) according to Crawford-Saffi classification, while 17 had infrarenal abdominal aortic aneurysms. There were 15 elective and four urgent procedures due to aneurismal rupture. The presence of the horseshoe kidney was detected in 16 patients before surgery (84.2%) by means of Duplex ultrasonography, angiography, computed tomography and intravenous urography. Multiple renal arteries were presented in 12 (63.2%) cases. A transperitoneal approach was used in 16 cases with abdominal aortic aneurysm, while left retroperitoneal approach with partial extrapleural removal of the 11th rib was performed in two cases of thoracoabdominal aneurysm and in one patient with AAA. In 18 cases, kidney tissue transection was successfully avoided with vascular graft placement beneath the horseshoe kidney. In one case only, the division of the renal isthmus was performed. In all 12 cases with detected anomalous renal arteries, their reattachment into vascular graft has been performed. Two patients (10.5%) died during perioperative period. One of them had ruptured type IV TAA. Seventeen patients who survived were followed from one to twenty years (mean 6.6 years). During the follow up period we lost track of 4 patients. In this period there were no signs of graft occlusion, or renal failure. CONCLUSION: Repair of an abdominal aortic aneurysm in the presence of the horseshoe kidney is a truly particular surgical challenge. It is associated with three main problems: choice of the surgical approach; the procedure regarding kidney isthmus preservation as well as recognition and reattachment of all significant anomalous renal arteries.


Subject(s)
Aneurysm, Ruptured/surgery , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation , Kidney/abnormalities , Kidney/blood supply , Renal Artery/abnormalities , Urogenital Abnormalities/complications , Vascular Malformations/complications , Aged , Aneurysm, Ruptured/complications , Aneurysm, Ruptured/diagnosis , Aneurysm, Ruptured/mortality , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Urogenital Abnormalities/diagnosis , Vascular Malformations/diagnosis
15.
Vasa ; 39(1): 77-84, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20186679

ABSTRACT

BACKGROUND: The objective of this study was to compare polyester (Dacron) and expanded polytetrafluorethilene (ePTFE) grafts for above-knee femoropopliteal bypass. PATIENTS AND METHODS: Eighty five patients with disabling claudications or limb threatening ischemia suitable for above-knee femoropopliteal reconstruction were randomized into two groups. In the first group the surgery was performed using 8 mm Dacron graft, whereas the patients in the second group were operated using ePTFE grafts. RESULTS: The primary patency rates for Dacron and ePTFE were 100 %, and 88.37 % (p < 0.05), while secondary patency rates were 83.3 % and 75 % (p > 0.05) respectively. The early limb salvage rates for Dacron and ePTFE were 100 % and 97.7 % (p > 0.05). Early (30-day) complications (bleeding 2.38 % and 2.32 %; wound infection 11.9 % and 11.63 %) occurred in both groups with similar frequency (p > 0.05). The patients were followed up over a period of 6 to 12 months (mean 8.3 +/- 3.6 months). The overall mortality rate in the follow-up period was 2.38 % (one patient) for Dacron and 6.98 % (three patients) for ePTFE group (p > 0.05). Late graft infection was noted in three patients (7.1 %) in Dacron, and two patients (4.65 %) in ePTFE group (p > 0.05). Primary patency rates were not significantly influenced by obesity, diabetes, hypertension, hyperlipidemia, cigarette smoking, (p > 0.05). However, poor run-off (only one crural artery patent on preoperative angiography) significantly decreased patency of both grafts and favored the use of ePTFE graft (p < 0.05). CONCLUSIONS: This study confirms that both materials are suitable for above-knee femoropopliteal reconstructions. Above-knee femoropopliteal bypass does not have a good long-term prognosis in the presence of poor run-off.


Subject(s)
Femoral Artery/surgery , Polyethylene Terephthalates/therapeutic use , Polytetrafluoroethylene/therapeutic use , Popliteal Artery/surgery , Aged , Cardiovascular Surgical Procedures , Female , Femur/blood supply , Humans , Knee Joint/blood supply , Knee Joint/surgery , Male , Postoperative Complications/epidemiology , Prospective Studies , Surgical Wound Infection/epidemiology , Treatment Outcome , Vascular Patency/physiology
17.
Injury ; 40(8): 815-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19523624

ABSTRACT

OBJECTIVE: The aim of the study was to identify factors influencing surgical treatment outcome following upper extremity arterial injuries. METHODS: This 15-year study (January 1992 to December 2006) included 167 patients with 189 civilian, iatrogenic or military upper extremity arterial injuries requiring surgical intervention. Patient data were prospectively entered into a vascular trauma database and retrospectively analysed. RESULTS: The most frequently damaged vessel was the brachial artery (55% of injuries), followed by the axillary (21.7%), antebrachial (21.2%) and subclavian (2.1%) arteries. Three primary amputations (1.8%) were performed because of extensive soft-tissue destruction and signs of irreversible ischaemia on admission. Seven secondary amputations (4.2%) were due to graft failure, infection, anastomotic disruption or the extent of soft-tissue and nerve damage. Fasciotomy was required in 9.6% of cases. Operative mortality was 2.4% (four deaths). Early graft failure, compartment syndrome, associated skeletal and brachial plexus damage and a military mechanism of injury were found to be significant risk factors for limb loss (p<0.01). CONCLUSION: Although careful physical examination should diagnose the majority of upper extremity arterial injuries, angiography is helpful in detailing their site and extent. Prompt reconstruction is essential for optimal results. Nerve trauma is the primary cause of long-term functional disability.


Subject(s)
Amputation, Surgical/statistics & numerical data , Ischemia/surgery , Upper Extremity/blood supply , Adolescent , Adult , Aged , Angiography , Axillary Artery/injuries , Brachial Artery/injuries , Child , Female , Humans , Ischemia/diagnosis , Ischemia/mortality , Male , Middle Aged , Popliteal Artery/injuries , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Upper Extremity/injuries , Vascular Patency , Young Adult
18.
J Cardiovasc Surg (Torino) ; 49(5): 619-25, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18670379

ABSTRACT

AIM: Several studies, comparing early and long-term results of the conventional carotid endarterectomy (CEA) and eversion carotid endarterectomy (EEA), were conducted for past 10 years. Nevertheless, it still remaining difficult to choose optimal endarterectomy technique. Choice yet mainly depends of experience of attending surgeon. The aim of this study was the comparison early and long-term results of the EEA and CEA. METHODS: Randomly, 103 patients were operated on in the eversion, and 98 patients in the conventional technique; 97 (48.3%) patients were asymptomatic and 104 (51.7%) had symptomatic lesions. All patients underwent preoperative cervical duplex scanning and neurological examination. The surgical procedure was carried out under general anesthesia. In cases with retrograde blood pressure less than 20 mmHg shunt was used; 78.6% of all CEA were finished up with ''patch'' angioplasty and 21.4% by primary suture. The primary outcomes were perioperative and late mortality, perioperative and late central neurological complications, a long-term survival rate and late restenosis incidence. RESULTS: The mean follow-up was 38 months. Mortality and long-term survival rate were similar in compared groups. The perioperative central neurological complications incidence were comparable in study groups (3.9% vs 12.1% , odds ratio 3.45, 95% confidence interval 1.1-11.1; P=0.029). The late restenosis incidence was significantly lower in eversion group (0.0% vs 6.1%). CONCLUSION: EEA has an advantage over the conventional procedure. The authors recommend CEA in cases when retrograde pressure indicated the use of the intraluminal shunting.


Subject(s)
Carotid Stenosis/surgery , Endarterectomy, Carotid/methods , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Postoperative Complications , Prospective Studies , Recurrence , Risk Factors , Survival Rate , Treatment Outcome
19.
Phlebology ; 23(4): 184-8, 2008.
Article in English | MEDLINE | ID: mdl-18663118

ABSTRACT

Aneurysms of the inferior vena cava (IVC) are extremely rare. To the best of our knowledge, only 29 cases of IVC aneurysms are published in literature. We present a new case of surgically treated symptomatic saccular aneurysm of the infrarenal IVC and review previously published cases. Following resection of the aneurysm and the thrombosed infrarenal IVC, the patient fully recovered. Thrombosed IVC aneurysm may mimic a retroperitoneal tumour. In some cases, CT and MRI findings may be equivocal. Surgical treatment is indicated in all symptomatic and low-risk asymptomatic cases.


Subject(s)
Aneurysm/pathology , Vena Cava, Inferior/pathology , Venous Thrombosis/pathology , Adult , Aneurysm/surgery , Humans , Male , Phlebography/methods , Tomography, X-Ray Computed , Treatment Outcome , Vascular Surgical Procedures , Vena Cava, Inferior/surgery , Venous Thrombosis/surgery
20.
J Med Genet ; 45(10): 679-85, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18628314

ABSTRACT

BACKGROUND: The Fragile X Mental retardation-Related 1 (FXR1) gene belongs to the fragile X related family, that also includes the Fragile X Mental Retardation (FMR1) gene involved in fragile X syndrome, the most common form of inherited mental retardation. While the absence of FMRP impairs cognitive functions, inactivation of FXR1 has been reported to have drastic effects in mouse and xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been identified, three of them being muscle specific. Interestingly, they encode FXR1P isoforms displaying selective RNA binding properties. METHODS AND RESULTS: Since facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy characterised by altered splicing of mRNAs encoding muscle specific proteins, we have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD patients. We show here that FSHD myoblasts display an abnormal pattern of expression of FXR1P isoforms. Moreover, we provide evidence that this altered pattern of expression is due to a specific reduced stability of muscle specific FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle specific isoforms. CONCLUSION: Our data suggest that the molecular basis of FSHD not only involves splicing alterations, as previously proposed, but may also involve a deregulation of mRNA stability. In addition, since FXR1P is an RNA binding protein likely to regulate the metabolism of muscle specific mRNAs during myogenesis, its altered expression in FSHD myoblasts may contribute to the physiopathology of this disease.


Subject(s)
Fragile X Mental Retardation Protein/metabolism , Muscular Dystrophy, Facioscapulohumeral/metabolism , RNA-Binding Proteins/metabolism , Alternative Splicing , Fragile X Mental Retardation Protein/chemistry , Fragile X Mental Retardation Protein/genetics , Gene Expression , Humans , Muscle Fibers, Skeletal/metabolism , Muscular Dystrophy, Facioscapulohumeral/genetics , Myoblasts/metabolism , Protein Isoforms/metabolism , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics
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