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1.
Diagnostics (Basel) ; 5(2): 254-71, 2015 Jun 19.
Article in English | MEDLINE | ID: mdl-26854152

ABSTRACT

Adrenal vein sampling (AVS) is the gold standard test to determine unilateral causes of primary aldosteronism (PA). We have retrospectively characterized our experience with AVS including concordance of AVS results and imaging, and describe the approach for the PA patient in whom bilateral AVS is unsuccessful. We reviewed the medical records of 85 patients with PA and compared patients who were treated medically and surgically on pre-procedure presentation and post-treatment outcomes, and evaluated how technically unsuccessful AVS results were used in further patient management. Out of the 92 AVS performed in 85 patients, AVS was technically successful bilaterally in 58 (63%) of cases. Either unsuccessful AVS prompted a repeat AVS, or results from the contralateral side and from CT imaging were used to guide further therapy. Patients who were managed surgically with adrenalectomy had higher initial blood pressure and lower potassium levels compared with patients who were managed medically. Adrenalectomy results in significantly decreased blood pressure and normalization of potassium levels. AVS can identify surgically curable causes of PA, but can be technically challenging. When one adrenal vein fails to be cannulated, results from the contralateral vein can be useful in conjunction with imaging and clinical findings to suggest further management.

2.
AJR Am J Roentgenol ; 203(3): 668-73, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25148174

ABSTRACT

OBJECTIVE: Stomal varices can cause life-threatening gastrointestinal hemorrhage in patients with portal hypertension. Optimal therapy is not well defined. The purpose of this study was to determine the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) creation for the treatment of hemorrhagic stomal varices. MATERIALS AND METHODS: All patients who underwent TIPS creation for hemorrhagic stomal varices refractory to medical or endoscopic therapy over a 20-year period (1992-2012) were included. Ten patients (mean age, 63 ± 12 years) were identified. Retrospective chart review was used to document demographic characteristics, procedure details, technical and clinical success, complications, recurrent hemorrhage, and need for repeat interventions. Patients underwent follow-up for an average of 2 years (range, 22 days-9.6 years). RESULTS: All patients had cirrhosis and portal hypertension. Average corrected sinusoidal pressures were 11 ± 2.4 mm Hg (range, 6-15 mm Hg) before TIPS placement and 4.3 ± 1.8 mm Hg (range, 2-8 mm Hg) after TIPS placement. Five patients (50%) underwent adjunctive embolization of stomal varices through the TIPS, which did not affect outcome. Complications included one patient each with a contrast allergy and renal failure. Six patients experienced complete resolution of bleeding without further intervention (60%). Four patients had recurrent stomal hemorrhage. Two of the four needed TIPS revision for occlusion; one underwent oversewing of the ostomy; and in one the hemorrhage resolved with conservative measures after confirmation of TIPS patency. CONCLUSION: TIPS creation, with or without adjunctive variceal embolization, is a safe and effective treatment of refractory hemorrhagic stomal varices. Reintervention for recurrent bleeding may be required and appears effective.


Subject(s)
Esophageal and Gastric Varices/surgery , Fibrosis/surgery , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Hypertension, Portal/surgery , Portasystemic Shunt, Transjugular Intrahepatic , Aged , Aged, 80 and over , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/diagnosis , Female , Fibrosis/complications , Fibrosis/diagnosis , Gastrointestinal Hemorrhage/diagnosis , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/etiology , Male , Middle Aged , Portal Pressure , Treatment Outcome
3.
J Vasc Interv Radiol ; 25(4): 556-60, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24507994

ABSTRACT

PURPOSE: To evaluate the indications, complications, and long-term results of translumbar port placements to the inferior vena cava for long-term central venous access in a single tertiary center. MATERIALS AND METHODS: This retrospective study included all patients with cancer who underwent translumbar port placement from January 2000 to July 2012; 31 patients (all women) with an average age of 53.1 years ± 11.1 (range, 30-77 y) were included in the study. Of these patients, 26 (81%) had breast cancer, 3 had lung cancer, 1 had ovarian cancer, and 1 had rectal cancer. Indications included central venous occlusion in 9 patients (29%) and bilateral mastectomy and lymph node dissection in 22 patients (71%). RESULTS: All procedures were technically successful. The overall 30-day complication rate was 9.7% (n = 3). Average catheter use was 14.1 months ± 21 (range, 0.75-108 mo). Thirteen (41.9%) ports were removed because they were no longer needed; 4 (12.9%) ports required removal for port malfunction; 12 (38.7%) patients died with their ports still in place; 2 (6.5%) ports remain in use. Three (9.7%) ports required delayed secondary intervention to remain functional. One patient had a systemic infection attributed to the port, resulting in an overall infection rate of 0.08 per 1,000 catheter days. CONCLUSIONS: Translumbar inferior vena cava port placement is a technically feasible and safe alternative method for long-term central venous access.


Subject(s)
Antineoplastic Agents/administration & dosage , Catheterization, Central Venous/instrumentation , Central Venous Catheters , Neoplasms/drug therapy , Vena Cava, Inferior , Administration, Intravenous , Adult , Aged , Boston , Catheterization, Central Venous/adverse effects , Device Removal , Equipment Design , Equipment Failure , Feasibility Studies , Female , Humans , Middle Aged , Radiography, Interventional , Retrospective Studies , Tertiary Care Centers , Time Factors , Tomography, X-Ray Computed
4.
Cardiovasc Intervent Radiol ; 37(2): 381-7, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23754191

ABSTRACT

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, patients with advanced stage (BCLC-C) hepatocellular carcinoma (HCC) are recommended for systemic treatment or palliative therapy. However, chemoembolization with drug-eluting beads (DEB-TACE) has been shown to be safe in high-risk patients. The purpose of our study was to evaluate the safety and effectiveness of DEB-TACE in patients with an advanced-stage HCC. METHODS: In this institutional review board-approved, retrospective study, 80 patients with advanced-stage HCC underwent DEB-TACE with doxorubicin. Patients were evaluated for median hospital stay, incidence of Grade 3/4 toxicities, 30-day mortality, progression-free survival (PFS), and overall survival (OS) following DEB-TACE. Univariate and multivariate analysis were performed for predictors of better OS. RESULTS: The median hospital stay following DEB-TACE was 1 day (range: 1-11). The median PFS and OS were 5.1 months [95% confidence interval (CI): 4.1-7.7] and 13.3 months (95% CI: 10.1-18.6) respectively. On multivariate analysis ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS. Patients with ECOG PS ≤ 1 demonstrated a median survival of 17.7 months compared with 5.6 months for patients with ECOG PS > 1 (p = 0.025). Multiple DEB-TACE procedures (>2 procedures) were associated with improved survival (26.8 months) compared with patients with one or two procedures (11.4 months, p = 0.01). Portal vein thrombosis or extrahepatic disease had no statistically significant association with OS. CONCLUSIONS: DEB-TACE is safe and effective in patients with advanced HCC. ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Doxorubicin/administration & dosage , Drug Carriers/administration & dosage , Liver Neoplasms/therapy , Aged , Analysis of Variance , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Palliative Care/methods , Patient Safety , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Survival Analysis , Time Factors , Treatment Outcome
5.
J Neurointerv Surg ; 6(7): 541-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24005126

ABSTRACT

Evaluation of the pathogenic mechanisms underlying Cushing disease (CD) is limited partly by the inaccessibility of the pituitary gland for biopsy. We used bilateral inferior petrosal sinus sampling (BIPSS), the gold standard in diagnosing pituitary sources of CD, to obtain central blood samples for in vivo metabolomic analysis of pathways involved in pituitary adenomas. We evaluated 16 samples from eight patients who underwent BIPSS to measure adrenocorticotropic hormone (ACTH) levels in the inferior petrosal sinus (IPS) bilaterally. Seven patients had CD with concordant BIPSS, surgical, and pathologic findings. Samples from the IPS contralateral to histologically proven lesions were used as controls. BIPSS of the eighth patient revealed no central pituitary ACTH source, and these samples were also included as controls. Plasma samples were profiled using a combination of three liquid chromatography tandem mass spectrometry methods, which assessed 259 metabolites. Following Bonferroni correction for multiple comparisons, three small compound biomarkers of CD (pyridoxate, deoxycholic acid, and 3-methyladipate) were identified to be significantly altered in pituitary adenomas. The pathway most significantly impacted in CD samples is one previously shown to be upregulated in other cancers. Exploiting the BIPSS technique, we showed a complete metabolite and lipid profile of pituitary adenomas in CD. These potential biomarkers of CD may elucidate tumor biology and suggest possible diagnostic molecular imaging probes as well as therapeutic targets in patients with recurrent disease after surgery.


Subject(s)
Adenoma/diagnosis , Biomarkers, Tumor/analysis , Petrosal Sinus Sampling/methods , Pituitary Neoplasms/diagnosis , Adenoma/metabolism , Adenoma/pathology , Adult , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Male , Metabolomics , Middle Aged , Pituitary ACTH Hypersecretion/pathology , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology
6.
J Vasc Interv Radiol ; 24(9): 1347-52, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23871695

ABSTRACT

PURPOSE: To compare the incidences of symptom recurrence and permanent amenorrhea following uterine artery embolization (UAE) for symptomatic fibroid tumors in patients with type I and II utero-ovarian anastomoses (UOAs) with versus without ovarian artery embolization (OAE). MATERIALS AND METHODS: A retrospective, institutional review board-approved study of 99 women who underwent UAE for symptomatic fibroid tumors from April 2005 to October 2010 was conducted to identify patients who had type I or II UOAs at the time of UAE. Based on the embolization technique, patients were categorized into standard (ie, UAE only), combined (ie, UAE and OAE), and control (patients without UOAs who underwent UAE) groups. Data collected included patient characteristics, procedural technique and findings, symptom recurrence, secondary interventions, and permanent amenorrhea. Statistical analysis was performed with the Fisher exact test, with significance reached at P < .05. RESULTS: Twenty patients (20.2%; mean age, 46.9 y ± 6.3) had type I (n = 3) or II (n = 17) UOAs. Thirteen (65%) underwent UAE only (standard group) and seven (35%) underwent UAE and OAE (combined group). There were no significant differences between groups in demographics or in the incidence of permanent amenorrhea after procedures (follow-up, 561 d ± 490). There was a significantly higher incidence of symptom recurrence in the standard group compared with the control group (P = .01), with no differences between combined and control groups (P = 1). CONCLUSIONS: There were no statistical differences in permanent amenorrhea rates in the groups studied, with significantly higher symptom recurrence rates observed when OAE was not performed in the setting of UOA.


Subject(s)
Amenorrhea/epidemiology , Leiomyoma/epidemiology , Leiomyoma/therapy , Uterine Artery Embolization/statistics & numerical data , Uterine Artery/diagnostic imaging , Uterine Neoplasms/epidemiology , Uterine Neoplasms/therapy , Amenorrhea/diagnostic imaging , Angiography/statistics & numerical data , Boston/epidemiology , Causality , Comorbidity , Female , Humans , Leiomyoma/diagnostic imaging , Middle Aged , Ovary/diagnostic imaging , Prevalence , Recurrence , Retrospective Studies , Risk Assessment , Treatment Failure , Treatment Outcome , Uterine Neoplasms/diagnostic imaging
7.
J Vasc Interv Radiol ; 24(8): 1201-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23735316

ABSTRACT

Although much attention has been paid to mechanisms of anticancer drug resistance that focus on intracellular processes that protect tumor cells, it has recently become increasingly evident that the unique features of the tumor microenvironment profoundly impact the efficacy of cancer therapies. The properties of this extracellular milieu, including increased interstitial pressure, decreased pH, hypoxia, and abnormal vascularity, result in limited drug efficacy; this finding is true not only for systemic chemotherapy but also for catheter-based therapies, including chemoembolization and radioembolization. The present review summarizes the barriers to drug delivery imposed by the tumor microenvironment and provides methods to overcome these hurdles.


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Medical Oncology/methods , Neoplasms/drug therapy , Radiography, Interventional , Animals , Antineoplastic Agents/pharmacokinetics , Biological Transport , Catheterization , Cell Hypoxia , Drug Resistance, Neoplasm , Humans , Hydrogen-Ion Concentration , Neoplasms/blood supply , Neoplasms/metabolism , Neoplasms/pathology , Permeability , Tissue Distribution , Treatment Outcome , Tumor Microenvironment
9.
Semin Dial ; 26(6): 728-32, 2013.
Article in English | MEDLINE | ID: mdl-23458207

ABSTRACT

Creating a vascular access in the presence of a cardiovascular implantable electronic device (CIED) in a patient with or approaching end-stage renal disease can be challenging. In this study, we aimed to evaluate the impact of a CIED on the outcomes of vascular access creation in hemodialysis patients and determine their effects on vascular access patency. This is a single-center retrospective review of hemodialysis patients who underwent vascular access creation after CIED placement. Outcomes of vascular access creation and need for endovascular interventions were compared between patients with vascular access created ipsilateral and contralateral to the site of CIED. Comparing patients with arteriovenous (AV) access created ipsilateral to CIED placement (n=19) versus the contralateral side (n=17), the primary failure rate was 78.9% versus 35.3% (p=0.02). For AV accesses that were matured, the median primary patency durations for AV accesses created ipsilateral to the CIED was 11.2 months compared to 7.8 months for AV accesses created contralateral to the CIED (p=1.00). AV accesses created ipsilateral to a CIED have a higher primary failure rate compared with the contralateral arm and should be avoided as much as possible.


Subject(s)
Arteriovenous Shunt, Surgical , Defibrillators, Implantable , Kidney Failure, Chronic/therapy , Pacemaker, Artificial , Renal Dialysis , Vascular Patency , Aged , Aged, 80 and over , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Vascular Access Devices
11.
Semin Thromb Hemost ; 39(4): 446-51, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23483455

ABSTRACT

Venous thrombosis is a major public health problem associated with significant morbidity and mortality and has a substantial impact on the quality of life. Over the years, it has become more apparent that anticoagulation alone in the treatment of deep venous thrombosis (DVT) is insufficient in the prevention of postthrombotic syndrome, which adversely impacts the quality of life of the patient, and it is insufficient in preventing recurrence of DVT. With the advent of innovative catheter designs to deliver thrombolytic therapies in the treatment of DVT, there have been significant advances in the management of DVT. We review the management of DVT with emphasis on catheter-directed interventions.


Subject(s)
Thrombolytic Therapy/methods , Venous Thrombosis/therapy , Catheters , Humans , Treatment Outcome
12.
Semin Thromb Hemost ; 39(4): 441-5, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23483456

ABSTRACT

Thrombotic or embolic arterial occlusive disease can lead to profound ischemia and, without emergent revascularization, is associated with significant morbidity and mortality. Significant advances in the management of arterial occlusive disease range from newer thrombolytic agents to innovative catheter designs to enhance thrombolysis and thrombectomy. Most of these advances have been directed toward the management of acute limb ischemia; therefore, we review the management of limb ischemia with emphasis on endovascular interventions.


Subject(s)
Ischemia/therapy , Leg/blood supply , Thrombolytic Therapy/methods , Thrombosis/therapy , Catheters , Humans , Thrombosis/surgery , Treatment Outcome
14.
Vasc Endovascular Surg ; 47(2): 97-101, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23315196

ABSTRACT

PURPOSE: To assess the feasibility and safety of intravascular ultrasound (IVUS) to guide inferior vena cava (IVC) filter placement using a single venous puncture technique. MATERIALS AND METHODS: Medical records of all patients who had IVC filters placed under IVUS guidance between January 1, 2005 and December 31, 2011 were retrospectively reviewed for pertinent history, results, and complications. All filters were placed using a single venous puncture technique. RESULTS: Filters were successfully placed within the IVC in 94% of the patients with 6 malpositioned filters (4 in the iliac veins and 2 in the suprarenal IVC). Complications included groin hematoma (4%), deep venous thrombosis at the site of vascular access (2%), and filter tilt >15° along the long axis of the IVC (2%). CONCLUSIONS: The IVUS-guided IVC filter placement using a single venous puncture technique is technically feasible and safe when compared to case series using a double venous puncture technique.


Subject(s)
Catheterization, Peripheral/methods , Prosthesis Implantation/instrumentation , Prosthesis Implantation/methods , Ultrasonography, Interventional , Vena Cava Filters , Vena Cava, Inferior/diagnostic imaging , Adult , Aged , Aged, 80 and over , Catheterization, Peripheral/adverse effects , Feasibility Studies , Humans , Middle Aged , Prosthesis Design , Prosthesis Implantation/adverse effects , Punctures , Retrospective Studies , Treatment Outcome , Ultrasonography, Interventional/adverse effects , Young Adult
15.
Diagn Interv Radiol ; 19(1): 44-8, 2013.
Article in English | MEDLINE | ID: mdl-22801870

ABSTRACT

PURPOSE: We aimed to evaluate the longitudinal stability of left common iliac vein (LCIV) compression by the right common iliac artery on magnetic resonance venography (MRV). MATERIALS AND METHODS: This retrospective study included 214 patients diagnosed with May-Thurner syndrome by MRV. We identified a subset of patients who underwent contrast-enhanced cross-sectional imaging of the pelvis six months before or anytime after the MRV and did not undergo any interventional venous procedures between the two studies; 36 patients met these criteria. The degree of venous compression was calculated in both the index and comparison study. RESULTS: On the index MRV, the mean compression of the LCIV was 62%. However, on the comparison study in the same patients, the mean compression was 39%. The mean change in degree of compression between the two studies was 23% (P < 0.0001), ranging from a 12% increase to 69% decrease in degree of compression on the comparison study. CONCLUSION: The compressed LCIV on a single MRV study was not stable over time and thus may be insufficient to diagnose May-Thurner syndrome.


Subject(s)
Magnetic Resonance Angiography/methods , May-Thurner Syndrome/diagnosis , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/pathology , Iliac Vein/diagnostic imaging , Iliac Vein/pathology , Male , Middle Aged , Phlebography/methods , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray Computed/methods , Young Adult
16.
J Vasc Access ; 14(2): 170-4, 2013.
Article in English | MEDLINE | ID: mdl-23080333

ABSTRACT

PURPOSE: To compare complication rates in patients who have port-a-catheters inserted and left accessed for immediate use and those who have ports inserted but not accessed. METHODS: In this retrospective, IRB-approved study, medical records of patients who received a port catheter between 9/2009 and 2/2010 were reviewed. The data collected included patient demographics, diagnosis, procedure and complications. The patients were categorized into two groups: accessed (patients in whom the port was accessed with a Huber needle for immediate intravenous use and the patient left the procedure area with needle indwelling) and control (patients in whom the ports were not accessed). Complications were classified according to Society of Interventional Radiology guidelines. Results are given as mean ±SD. Statistical analysis was performed with student t test and statistical significance was considered at P<.05. RESULTS: A total of 467 ports were placed in 465 patients (Men: 206); 10.7% in the accessed group (n=50, age: 60±13.9) and 89.3% in the control group (n=417, age: 59±13.5). There were no statistically significant differences in patient demographics between the groups. The overall complication rate was 0.6% (n=3). Two complications (hematoma causing skin necrosis and thrombosis of the port) occurred in the control group and one (infection) in the accessed group. Infection rates after procedures were 2% (1/50) in the accessed group and 0% (0/417) in the control group. There was no statistically significant difference in overall complication (P=.1) and infection (P=.1) rates among the groups. CONCLUSIONS: Leaving the port accessed immediately after placement does not increase the risk of infection or other complications.


Subject(s)
Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/instrumentation , Central Venous Catheters/adverse effects , Prosthesis-Related Infections/etiology , Radiography, Interventional , Renal Dialysis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Young Adult
17.
Vasc Endovascular Surg ; 47(1): 24-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23143226

ABSTRACT

OBJECTIVES: To evaluate the safety and efficacy of Option inferior vena cava (IVC) filter during placement and short-term follow-up. METHODS: A total of 165 patients (mean age: 60-years) who received Option IVC filter from June 2009 to July 2011 were included. In all, 42 patients presented with deep vein thrombosis (DVT), 26 with pulmonary embolism (PE), and 17 with both. All outcomes were examined until April 30, 2012. RESULTS: The filters were successfully deployed in 161patients. During follow-up (mean, 9.5 ± 0.68months), 10 patients were diagnosed with post-filter PE and 13 patients with DVT. There were no instances of fatal PE. Follow-up abdominal computed tomography was available in 60 patients and demonstrated filter-related problems in 8 patients (2: penetration of filter legs, 5: asymptomatic nonocclusive thrombus, and 1: caval occlusion). There were no instances of filter migration or fracture. In total, 27 filters were successfully retrieved after a mean of 5.27 ± 0.76 months. CONCLUSION: The Option filter was effective and safe during implantation and short-term follow-up and associated with high technical success at retrieval.


Subject(s)
Prosthesis Implantation/instrumentation , Pulmonary Embolism/therapy , Vena Cava Filters , Venous Thrombosis/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Device Removal , Female , Humans , Male , Middle Aged , Prosthesis Design , Prosthesis Implantation/adverse effects , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Venous Thrombosis/complications , Venous Thrombosis/diagnosis , Young Adult
18.
Diagn Interv Radiol ; 19(2): 173-80, 2013.
Article in English | MEDLINE | ID: mdl-23233402

ABSTRACT

Critical limb ischemia (CLI) is a growing epidemic with bleak patient outcomes. A variety of treatment modalities have been adopted to address CLI based on comorbidities, life expectancy, and the nature of the arterial disease. With advances in technology and treatment strategies, the clinical outcomes of CLI patients have significantly improved over recent years. However, despite progress, patency rates of both surgical and endovascular interventions, limb-salvage and amputation rates are still dismal. We review the epidemiology, treatment strategies, imaging modalities, and the microcirculation aspect of CLI.


Subject(s)
Diagnostic Imaging/methods , Lower Extremity/blood supply , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/therapy , Radiology, Interventional/methods , Endovascular Procedures/methods , Humans , Lower Extremity/surgery , Microcirculation , Risk Factors , Vascular Patency
20.
J Vasc Interv Radiol ; 23(5): 712-8, 2012 May.
Article in English | MEDLINE | ID: mdl-22525027

ABSTRACT

PURPOSE: Mechanisms underlying transition of a thrombus susceptible to tissue plasminogen activator (TPA) fibrinolysis to one that is resistant is unclear. Demonstration of a new possible thrombus scaffold may open new avenues of research in thrombolysis and may provide mechanistic insight into thrombus remodeling. MATERIALS AND METHODS: Ten human thrombus samples were collected during cases of thrombectomy and open surgical repair of abdominal aortic aneurysms (five samples < 3 d old and five samples > 1 y old). Additionally, an acute murine hindlimb ischemia model was created to evaluate thrombus samples in mice. Human sections were immunostained for the H2A/H2B/DNA complex, myeloperoxidase, fibrinogen, and von Willebrand factor. Mouse sections were immunostained with the H2A antibody. All samples were further evaluated after hematoxylin and eosin and Masson trichrome staining. RESULTS: An extensive network of extracellular histone/DNA complex was demonstrated in the matrix of human ex vivo thrombus. This network is present throughout the highly cellular acute thrombus. However, in chronic thrombi, detection of the histone/DNA network was predominantly in regions of low collagen content and high cell density, which were mostly near the lumen. These regions of high cell density contained neutrophils and monocytes. Similarly, sections from the acute murine hindlimb ischemia model also exhibited extensive immunoreactivity to the histone antibody in the extracellular space within murine thrombi. CONCLUSIONS: Extensive detection of genomic DNA associated with histones in the extracellular matrix of human and mouse thrombi suggest the presence of a new thrombus-associated scaffold.


Subject(s)
DNA/metabolism , Deoxyribonucleases/therapeutic use , Fibrinolytic Agents/therapeutic use , Histones/metabolism , Muscle, Skeletal/blood supply , Thrombolytic Therapy/methods , Thrombosis/drug therapy , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Animals , Aortic Aneurysm, Abdominal/complications , Disease Models, Animal , Extracellular Matrix Proteins/metabolism , Female , Hindlimb , Humans , Immunohistochemistry , Ischemia/complications , Laser-Doppler Flowmetry , Male , Mice , Middle Aged , Monocytes/metabolism , Neutrophils/metabolism , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/genetics , Thrombosis/metabolism , Time Factors , Tomography, X-Ray Computed
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