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1.
J Nanopart Res ; 17(8)2015 Aug.
Article in English | MEDLINE | ID: mdl-26594129

ABSTRACT

Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle.

2.
J Vasc Surg ; 33(4): 783-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11296332

ABSTRACT

PURPOSE: Treatment for primary subclavian-axillary vein thrombosis (SAVT) at our institution consists of thrombolysis and anticoagulation for 3 months. Thoracic outlet decompression has been performed for a small number of patients. We wanted to review the functional outcomes of patients treated in such a manner. MATERIAL AND METHODS: The records of all patients treated for a first episode of SAVT at our hospital over the past 10 years were reviewed. Demographics, comorbidities, method of diagnosis, and treatment for SAVT were recorded. Long-term follow-up was obtained by chart review and asking patients to complete the DASH (disabilities of the arm, shoulder and hand) questionnaire that was developed by the American Academy of Orthopedic Surgeons. RESULTS: Twenty-eight patients, 20 men and eight women, with a mean age of 36 were treated during the study period. The median time between onset of symptoms and treatment was 5.5 (range, 1-100) days. All patients had confirmation of the diagnosis by venography. Twenty-five patients received thrombolytic treatment with catheter-directed infusions of urokinase; in the other three patients the vein was chronically occluded. Twelve patients had some degree of residual stenosis and were treated with percutaneous transluminal angioplasty after thrombolysis. During the study period two patients underwent decompressive surgery. Twenty-one patients responded to the DASH questionnaire a mean of 2.9 years (range, 2 months to 8 years) after the episode of SAVT. Six (28%) of 21 patients were completely symptom free, 13 patients (62%) had DASH scores consistent with mild symptoms, and two patients had more severe symptoms. Twenty percent (4 of 21) of patients report some difficulty with work. CONCLUSIONS: Thrombolysis, followed by selective thoracic outlet decompression on the basis of the severity of patients' symptoms can be used as a therapeutic approach to SAVT without undue morbidity. The DASH questionnaire is a useful tool to evaluate results after therapy for SAVT.


Subject(s)
Axillary Vein , Decompression, Surgical , Subclavian Vein , Thrombolytic Therapy , Venous Thrombosis/therapy , Adult , Angioplasty, Balloon , Axillary Vein/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Plasminogen Activators/therapeutic use , Radiography , Recovery of Function , Subclavian Vein/diagnostic imaging , Urokinase-Type Plasminogen Activator/therapeutic use , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/surgery
3.
Am J Surg ; 181(1): 30-5, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11248173

ABSTRACT

BACKGROUND: We have previously reported preoperative and immediate postoperative formulae to estimate mortality in patients with ruptured abdominal aortic aneurysms (rAAA). In this study, we prospectively compared these formulae in patients with rAAA with their actual outcomes. METHODS: Information was collected on 134 patients from two centers over a 3-year period. Preoperative mortality risk was estimated using coefficients for age, level of consciousness, and cardiac arrest. Mortality risk in the immediate postoperative state was based on the presence of coagulopathy, ischemic colitis, prolonged requirement for inotropes, time from arrival at hospital to surgery, patient age, perioperative myocardial infarction, renal failure, and pre-operative hemoglobin level. RESULTS: The average age was 73 years (range 30 to 92 y) and 20 of 134 (15%) patients were women. Sixty-three patients (47%) survived. For patients with a calculated preoperative mortality risk of >90%, the sensitivity, specificity, and positive and negative predictive values were 25%, 98%, 95%, and 54%, respectively. For a mortality risk >80%, these values were 37%, 94%, 87%, and 57%, respectively. For patients with an estimated immediate postoperative mortality risk > or = 90%, the sensitivity, specificity, and positive and negative predictive values were 17%, 87%, 60%, and 49%, respectively. For a predicted mortality > or = 80%, these values were 22%, 84%, 60%, and 50%, respectively. CONCLUSIONS: Our formula for predicting mortality for preoperative rAAA patients may be useful for patients with an estimated mortality risk >/=90%, based on the high positive predictive value. The formula for immediate postoperative rAAA patients was not useful in predicting death.


Subject(s)
Aortic Aneurysm, Abdominal/mortality , Aortic Rupture/mortality , Aged , Female , Hospital Mortality , Humans , Logistic Models , Male , Postoperative Period , Predictive Value of Tests , Risk Assessment , Risk Factors , Sensitivity and Specificity
4.
Ann Vasc Surg ; 14(6): 648-51, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11128461

ABSTRACT

We describe a case of axillary vein thrombosis secondary to unusual venous anatomy. A patient with a strictured left-sided superior vena cava and axillary vein thrombosis was successfully treated with thrombolysis. The underlying stricture was treated with angioplasty and stenting.


Subject(s)
Axillary Vein/diagnostic imaging , Thrombosis/therapy , Vena Cava, Superior/abnormalities , Angiography , Angioplasty, Balloon , Constriction, Pathologic/congenital , Humans , Male , Middle Aged , Stents , Thrombolytic Therapy , Thrombosis/diagnostic imaging , Tomography, X-Ray Computed , Vena Cava, Superior/diagnostic imaging
5.
Cardiovasc Surg ; 8(6): 441-5, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10996097

ABSTRACT

PURPOSE: The purpose of this study was to determine the safety and efficacy of carotid endarterectomy (CEA) in octogenerians. METHODS: The records of 59 CEA performed in 57 patients who were 80yr or older between April 1993 and September 1998 were reviewed. There were 33 males and 24 females with a mean age of 82. Forty-nine procedures (83%) were performed for symptomatic carotid stenosis. The perioperative mortality and morbidity including neurological events were recorded. Long term follow-up data was also obtained. RESULTS: There were three perioperative deaths (5.1%) and three perioperative neurological events, including one stroke (1.7%) and two transient ischemic attacks (3.4%). The combined mortality and stroke rate was 6.8%. With a mean follow-up of 25+/-21months, Kaplan-Meier estimates of the 4-yr survival rate, freedom from stroke, and stroke free survival were 78, 94 and 75% respectively. For comparison, during the same time period, the same group of surgeons performed 597 CEA in patients less than 80yr of age. The perioperative mortality and stroke rate was 0.3 and 2.5% respectively, with a combined mortality and stroke rate of 2.7%. Perioperative mortality was significantly higher in patients over 80yr of age (P<0.01). CONCLUSIONS: CEA in octogenerians is associated with a higher mortality rate than in younger patients. However, good long term survival and freedom from stroke make CEA beneficial in octogenerians. With careful patient selection and perioperative management, CEA in octogenerians is worthwhile and should be advised in selected patients.


Subject(s)
Carotid Stenosis/surgery , Endarterectomy, Carotid , Postoperative Complications , Age Factors , Aged , Aged, 80 and over , Carotid Stenosis/complications , Female , Follow-Up Studies , Humans , Male , Postoperative Complications/mortality , Risk Factors , Stroke/etiology , Stroke/prevention & control
6.
J Invest Surg ; 13(3): 153-9, 2000.
Article in English | MEDLINE | ID: mdl-10933111

ABSTRACT

Benzoporphyrin derivative monoacid ring A (Verteporfin, BPD-MA), a photosensitizing drug, has been suggested as having inhibitory effects on smooth muscle cell (SMC) proliferation in rabbit aortic intimal injuries. The effect of BPD-MA on vascular SMCs in the absence of light stimulation in vitro and in vivo was studied using models of intimal hyperplasia. Human SMCs were incubated with BPD-MA for 4 h in darkness. A small (20%) but significant decrease in viability (n =42,p < .05) was noted for BPD-MA concentrations above 15 microg/mL. This was an all-or-none phenomenon with no further decrease in viability at higher concentrations. Treatment with BPD-MA was also carried out in vivo using a balloon injury model of intimal hyperplasia in rabbit aortas. Thirty-three rabbits were randomized into five groups and given intravenous BPD-MA (2 mg/kg) according to the following schedule: Group 1 (n = 8), BPD-MA 25 min prior to injury; Group 2 (n = 8), BPD-MA 25 min prior to injury plus a second dose 4 weeks later; Group 3 (n = 4), BPD-MA immediately postinjury; Group 4 (n = 7), BPD-MA immediately postinjury plus a second dose 4 weeks later; or Group 5 (n = 6), no drug (control group). No statistically significant difference was seen in the amount of intimal hyperplasia that developed in the five groups.


Subject(s)
Aorta/injuries , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Angioplasty, Balloon/adverse effects , Animals , Aorta/pathology , Cell Division/drug effects , Cells, Cultured , Disease Models, Animal , Humans , Hyperplasia , In Vitro Techniques , Mammary Arteries/cytology , Photic Stimulation , Rabbits , Tunica Intima/drug effects , Tunica Intima/pathology , Verteporfin
7.
Am J Physiol Heart Circ Physiol ; 278(6): H1815-22, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10843877

ABSTRACT

In animal models the somatostatin analog angiopeptin inhibits intimal hyperplasia by acting primarily through somatostatin receptor 2 (SSTR-2). However, the results of clinical trials using angiopeptin have been disappointing. In this study we showed that human blood vessels express high levels of SSTR-1 with significantly lower levels of SSTR-2 and -4. Samples of normal veins and arteries, as well as atherosclerotic arteries, expressed predominantly SSTR-1. In addition, the levels of SSTR-1 varied between individuals, indicating that the vascular disease process may have affected SSTR gene expression. Immunocytochemical studies demonstrated that SSTR-1 was present in endothelial but not vascular smooth muscle cells. No evidence of SSTR-3 or -5 expression was detected in normal or diseased blood vessels. Two endothelial cell preparations, ECV304 and human umbilical vein endothelial cells, were investigated and shown to express only SSTR-1 and -4. Exposure of these cells to 10 nM somatostatin or 10 nM SSTR-1-specific agonist resulted in alterations to the actin cytoskeleton, as characterized by a loss of actin stress fibers coupled with an increase in lamellipodia formation at the plasma membrane. These results suggest that the lack of effectiveness of angiopeptin in humans may be due to the differential expression of SSTR-1 by human endothelial cells.


Subject(s)
Endothelium, Vascular/metabolism , Receptors, Somatostatin/physiology , Arteriosclerosis/metabolism , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Hormones/pharmacology , Humans , Immunohistochemistry , Protein Isoforms/metabolism , Protein Isoforms/physiology , Receptors, Somatostatin/metabolism , Reference Values , Somatostatin/pharmacology
8.
Surgery ; 127(5): 577-83, 2000 May.
Article in English | MEDLINE | ID: mdl-10819068

ABSTRACT

BACKGROUND: The somatostatin analog, angiopeptin, inhibits intimal hyperplasia formation; although the specific somatostatin receptor (SSTR) subtypes transducing this effect are unknown. The purpose of this study was to determine the expression of SSTR subtypes in rat iliac arteries after balloon catheter endothelial injury and perivascular dissection. METHODS: Male rats received balloon endothelial injury to their left common and external iliac arteries with or without circumferential arterial dissection. The right arteries served as controls. At 1 and 2 months after intimal injury, animals were killed and their iliac arteries harvested and studied for SSTR expression by using immunocytochemical and molecular techniques. Quantitative polymerase chain reaction was used to determine the level of SSTR expression. RESULTS: Normal rat iliac arteries expressed only SSTR2 and 3. After balloon endothelial injury, there was significant upregulation of SSTR2 messenger RNA at 1 and 2 months after injury as compared with controls (1 month, 1.8 +/- 0.3 vs 0.4 +/- 0.1 zmol, P < .001; 2 months, 2.7 +/- 0.5 vs 1.1 +/- 0.2 zmol, P < .001). The addition of adventitial dissection to endothelial injury also showed a significant increase in SSTR2 expression (1 month, 2.4 +/- 0.4 vs 0.8 +/- 0.2, P < .05; 2 months, 1.3 +/- 0.3 vs 0.7 +/- 0.3, P < .05), but not significantly greater than that seen after balloon endothelial injury alone. Immunocyto-chemical studies also demonstrated an increase in SSTR2 immunoreactivity on the luminal surface of the endothelial cells in the balloon catheter-injured arteries. CONCLUSIONS: These findings show that SSTR2 is the primary SSTR that is upregulated after injury and likely mediates the effects of somatostatin analogs on intimal hyperplasia.


Subject(s)
Endothelium, Vascular/physiology , Iliac Artery/chemistry , Iliac Artery/surgery , Receptors, Somatostatin/analysis , Animals , Immunohistochemistry , Male , RNA, Messenger/analysis , Rats , Rats, Wistar , Receptors, Somatostatin/classification , Receptors, Somatostatin/genetics , Reverse Transcriptase Polymerase Chain Reaction
9.
Can J Surg ; 43(2): 105-11, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10812344

ABSTRACT

OBJECTIVES: To assess patient waiting times for vascular surgery and to determine if complications of the disease develop while the patients are awaiting surgery. DESIGN: Prospective cohort study. SETTING: A university-affiliated tertiary care institution. PATIENTS: All 554 patients who underwent scheduled vascular surgical procedures between April 1995 and October 1996. OUTCOME MEASURES: A literature review carried out to develop guidelines for acceptable waiting times for surgery associated with various vascular disorders based on their natural history (benchmark target); actual waiting times, defined as the interval from the date each patient was booked for surgery to the date of admission to hospital for the procedure; the proportion of patients admitted within the benchmark targets; and whether prolonged waiting time placed patients at risk for complications of their disease. RESULTS: Of the 554 patients, 382 (69%) were admitted within the benchmark waiting times. Of 84 patients having an abdominal aortic aneurysm, the aneurysm ruptured during the waiting period in 6, and 4 of them died, for a complication rate of 7% and a death rate of 5%. Two of the 6 aneurysms ruptured after the patient had waited longer than the target time. Three of 100 patients with symptomatic carotid artery stenosis awaiting admission for carotid endarterectomy suffered ischemic stroke, for a 3% complication rate; all had waited longer than the target period. One patient suffered occlusion of a femoropopliteal bypass graft while awaiting revision of a stenosed bypass graft. CONCLUSIONS: This study suggests that although most patients are admitted for operation within the benchmark time, one-third are admitted late and may suffer serious complications of their disease while awaiting admission for the procedure.


Subject(s)
Patient Admission/statistics & numerical data , Vascular Diseases/complications , Vascular Diseases/surgery , Vascular Surgical Procedures/statistics & numerical data , Waiting Lists , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/surgery , Arteriovenous Shunt, Surgical , Benchmarking , British Columbia/epidemiology , Carotid Stenosis/complications , Carotid Stenosis/surgery , Disease Progression , Health Services Research , Hospitals, University , Humans , Peripheral Vascular Diseases/complications , Peripheral Vascular Diseases/surgery , Practice Guidelines as Topic , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome
10.
Ann Vasc Surg ; 13(6): 566-70, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10541607

ABSTRACT

The purpose of this study was to determine the efficacy of intraoperative intraarterial urokinase (UK) in patients who suffered an acute stroke immediately following carotid endarterectomy (CEA). From January 1995 to March 1998, 823 carotid endarterectomies were performed. The subsequent results showed that intraarterial UK in the setting of early post-CEA neurologic events appears to be safe and may be a useful adjunct to re-exploration in improving neurologic outcomes.


Subject(s)
Endarterectomy, Carotid/adverse effects , Plasminogen Activators/administration & dosage , Stroke/surgery , Thrombolytic Therapy , Urokinase-Type Plasminogen Activator/administration & dosage , Aged , Carotid Artery, Internal , Combined Modality Therapy , Female , Humans , Infusions, Intra-Arterial , Intraoperative Care , Male , Middle Aged , Retrospective Studies , Stroke/drug therapy , Stroke/etiology
12.
J Vasc Surg ; 29(6): 986-94, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10359932

ABSTRACT

PURPOSE: The North American Symptomatic Carotid Endarterectomy Trial (NASCET) showed that selected patients benefited from surgery when their carotid artery was 50% or more stenosed. This study assessed the accuracy of color-flow duplex ultrasound scanning (DUS) parameters to detect 50% or greater carotid artery stenosis and to determine the situations in which carotid endarterectomy (CEA) without angiography could be justified. METHODS: From March 1, 1995, to December 1, 1995, all patients considered for CEA were studied with DUS and carotid angiography. Results of the two tests were blindly compared. DUS measurements of internal carotid artery (ICA) peak systolic velocity (PSV), end diastolic velocity, and ratio of the ICA to common carotid artery PSV (ICA/CCA) were subjected to receiver operator characteristic curve analysis to determine the most accurate criterion predicting 50% or greater angiographic stenosis. The criterion for identifying patients for CEA without angiography was selected from criteria with a high positive predictive value (PPV) and sensitivity. RESULTS: A total of 188 carotid bifurcations were available for comparison. A PSV (ICA/CCA) of 2 or higher was the most accurate criterion for detection of 50% or greater stenosis, with an accuracy rate of 93% (sensitivity, 96%; specificity, 89%; PPV, 92%). A PSV (ICA/CCA) of 3.6 or higher was the best criterion for identifying candidates for CEA who had not undergone earlier angiography, with PPV, sensitivity, specificity, and accuracy rates of 98%, 77%, 98%, and 86%, respectively. CONCLUSION: These redefined criteria detect the NASCET-defined threshold level of 50% or greater ICA stenosis, above which CEA results in stroke reduction. A management algorithm based on these criteria should help to minimize both angiography and unnecessary intervention.


Subject(s)
Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Endarterectomy, Carotid/standards , Ultrasonography, Doppler, Color/standards , Algorithms , Angiography , Blood Flow Velocity , Carotid Stenosis/physiopathology , Diagnosis, Differential , Humans , ROC Curve , Sensitivity and Specificity , Systole , United States
13.
Ann Vasc Surg ; 12(3): 244-7, 1998 May.
Article in English | MEDLINE | ID: mdl-9588510

ABSTRACT

This study prospectively compared the accuracy of published duplex ultrasonographic criteria for 70%-99% internal carotid artery (ICA) stenosis according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method to determine angiographic stenosis. From March 1, 1995 to December 1, 1995, all patients considered for carotid endarterectomy (CEA) were studied with carotid duplex ultrasound and carotid angiography within 1 month of the ultrasound study. Duplex measurements of ICA peak systolic velocity (PSV), end diastolic velocity (EDV), and ratio of the ICA to common carotid artery (CCA) PSVs were recorded. Degree of stenosis on angiography was determined using NASCET criteria. A MEDLINE search to identify duplex ultrasound criteria to predict NASCET defined 70%-99% ICA stenosis was carried out. In addition, the original University of Washington criteria for critical stenosis (> or = 80%) was also examined. The accuracy of these criteria was determined with angiographic results and the positive predictive value (PPV) of each criterion were compared. Ninety-nine patients with 185 carotid bifurcations were available for comparison. The different duplex criteria for determining NASCET defined 70%-99% ICA stenosis were: ICA PSV > 175 cm/sec or PSV < 40 cm/sec, PSV > 230 cm/sec, ratio of ICA to CCA PSVs > 4, PSV > 130 cm/sec plus EDV > 100 cm/sec, and PSV > 270 cm/sec plus EDV > 110 cm/sec. When compared with angiography, the calculated PPVs for these criteria were 71% (73/103), 81% (71/88), 86% (67/78), 88% (62/70), and 90% (57/63), respectively. The University of Washington criteria for critical stenosis (PSV > 125 cm/sec plus EDV > 135 cm/sec) had the highest PPV at 91.6% (55/60). The University of Washington criteria for critical stenosis had the highest PPV to predict a 70%-99% angiographic stenosis.


Subject(s)
Carotid Stenosis/diagnostic imaging , Ultrasonography, Doppler, Duplex , Blood Flow Velocity/physiology , Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/classification , Carotid Stenosis/surgery , Diastole/physiology , Endarterectomy, Carotid , Humans , Sensitivity and Specificity , Systole/physiology
14.
Photochem Photobiol ; 65(5): 877-83, 1997 May.
Article in English | MEDLINE | ID: mdl-9155261

ABSTRACT

In this study we compared the plasma distribution and arterial accumulation of a photosensitizer, benzoporphyrin derivative (BPD), in two models of atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer by the abnormal portion of a vessel is a necessity in order for photodynamic therapy to become a successful modality for inhibition of intimal hyperplasia, selective removal of atherosclerotic tissue or imaging of diseased arteries. Liposome-based formulations were compared to freshly isolated native low density lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD. Plasma distribution of the photosensitizer was analyzed by KBr density gradient ultracentrifugation. Although the delivery vehicle influenced plasma distribution immediately postinjection, BPD subsequently partitioned according to the plasma concentration of the lipoproteins. Photosensitizer level in plaque and normal artery specimens was determined by ethyl acetate extraction and spectrofluorometric measurement. The measurement of BPD in normal and atherosclerotic arterial tissue demonstrated a selective accumulation in atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of 2.8 and 4.1 were achieved, respectively). These results indicate that the preferential uptake of BPD by atherosclerotic plaque can be enhanced by preassociation with plasma lipoproteins, suggesting that light activation could lead to a highly selective destruction of diseased vascular tissue.


Subject(s)
Arteriosclerosis/pathology , Hyperlipidemias/pathology , Photosensitizing Agents/pharmacokinetics , Porphyrins/pharmacokinetics , Angioplasty , Animals , Arteriosclerosis/blood , Arteriosclerosis/metabolism , Cholesterol, Dietary/adverse effects , Drug Delivery Systems , Endothelium, Vascular/metabolism , Enzyme Inhibitors/metabolism , Hyperlipidemias/blood , Hyperlipidemias/metabolism , Lipoproteins, LDL/metabolism , Liposomes , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/blood , Phototherapy/methods , Porphyrins/administration & dosage , Porphyrins/blood , Rabbits
15.
Cardiovasc Surg ; 5(2): 150-6, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9212200

ABSTRACT

The purpose of this study was to examine the changing trends in surgical management of patients with abdominal aortic aneurysms at a tertiary care teaching hospital over the past 40 years, by analysis of demographic data, perioperative variables and outcomes on all patients having abdominal aortic aneurysm surgery between 1955 and 1993. Some 1604 abdominal aortic aneurysms were assessed. The annual rate of abdominal aortic aneurysm surgery increased from 17.6 to 67.8 cases per year. The non-ruptured to ruptured abdominal aortic aneurysm ratio increased from 2.4:1 in the first decade to 3.4:1 in the last 5 years. In non-ruptured abdominal aortic aneurysm repairs, the following variables changed over the four decades: patients age over 80 years increased (2.4% to 8.0%; P<0.04), concomitant lower-limb occlusive disease increased (12.2% to 23.7%; P<0.02), prevalence of smaller aneurysms (4-6 cm) increased (16.0% to 54.2%; P<0.0001); intraoperative hypotension decreased (9.0% to 0.7%; P<0.0001), postoperative hemorrhage decreased (8.2% to 0.0%, P<0.0001), postoperative leg ischemia decreased (5.7% to 1.1%; P<0.02) and postoperative amputation rate decreased (3.2% to 0.0%; P<0.03). There was a significant decrease in perioperative mortality (17.0% to 3.4%; P<0.0001). For ruptured aneurysms, early operation (within 1 h of admission) increased from 8.7% to 55.8% (P<0.0001), prevalence of intraoperative hypotension decreased (50.0% to 23.5%; P<0.001), and major venous injury decreased (18.0% to 5.2%; P<0.05). Mortality, however, did not decrease significantly (54.2% to 44.2%; P=0.32). In conclusion, there was a significant decrease in mortality and morbidity associated with non-ruptured abdominal aortic aneurysm repair over the four decades studied. In addition, older patients with smaller aneurysms and more co-morbid conditions were operated on during this period. Mortality for patients operated on for ruptured abdominal aortic aneurysm repair has not changed significantly.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Aortic Rupture/diagnosis , Aortic Rupture/mortality , Blood Vessel Prosthesis/statistics & numerical data , British Columbia , Comorbidity , Hospital Mortality , Hospitals, Teaching/statistics & numerical data , Humans , Intraoperative Complications/diagnosis , Intraoperative Complications/mortality , Intraoperative Complications/surgery , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Postoperative Complications/surgery , Risk Factors , Survival Rate , Treatment Outcome
16.
Biochem Pharmacol ; 53(7): 1019-27, 1997 Apr 04.
Article in English | MEDLINE | ID: mdl-9174116

ABSTRACT

Camptothecins are antineoplastic drugs that specifically target the enzyme DNA topoisomerase I. Prior work has identified a human topoisomerase I mutation, F361S, that confers resistance to camptothecin. We now demonstrate that substitutions in the 361-364 region can alter DNA cleavage/ligation by the enzyme. The defective catalysis exhibited by certain mutants likely relates to an impaired interaction with DNA, since these enzymes are more sensitive to the inhibitory effects of DNA binding ligands. Moreover, studies with peptides and fusion proteins suggest that the 361-364 region may bind DNA directly. The finding that the 361-364 region is involved in both enzyme catalysis and camptothecin resistance suggests that this region is part of the active site of human topoisomerase I and that camptothecin may interact with the enzyme at this site.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/pharmacology , DNA Topoisomerases, Type I/metabolism , Binding Sites , Catalysis , DNA/metabolism , DNA Damage , DNA Topoisomerases, Type I/biosynthesis , DNA Topoisomerases, Type I/genetics , Drug Resistance/genetics , Genetic Vectors , Humans , Mutation
17.
J Invest Surg ; 10(1-2): 17-23, 1997.
Article in English | MEDLINE | ID: mdl-9100170

ABSTRACT

Somatostatin is a general inhibitory hormone that exerts its effects through five functionally distinct receptor subtypes (SSTR1-5). Somatostatin analogues have been shown to be effective in inhibiting intimal hyperplasia after balloon induced vascular injury. However, the exact SSTR subtype responsible for the inhibitory effect of somatostatin on intimal hyperplasia is unknown. The purpose of this study was to define the presence and abundance of SSTR subtypes in a rat iliac balloon injury model of intimal hyperplasia. Transaortic balloon injury of the rat iliac artery was carried out. Rats were sacrificed at 48 h, 1 week, and 1 month postinjury, and perfusion fixed and stained with antibodies against SSTR2, 3, and 5. SSTR2 was identified on the intimal surfaces of normal and injured vessels. SSTR2 immunoreactivity was more prominent at 1 week and 1 month postinjury compared with 48 h postinjury. There was no immunostaining with SSTR3 and SSTR5 antibodies. The results show that SSTR2 is expressed on endothelial cells in normal and injured rat vessels. Its abundance in the injured vessel was increased up to 1 month postinjury.


Subject(s)
Catheterization/adverse effects , Iliac Artery/injuries , Receptors, Somatostatin/biosynthesis , Tunica Intima/pathology , Animals , Antibodies, Monoclonal , Biomarkers , Endothelium, Vascular/chemistry , Endothelium, Vascular/innervation , Iliac Artery/innervation , Iliac Artery/ultrastructure , Male , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/immunology , Peripheral Nerves/chemistry , Rats , Rats, Wistar , Receptors, Somatostatin/analysis , Receptors, Somatostatin/immunology , Thiolester Hydrolases/analysis , Thiolester Hydrolases/immunology , Time Factors , Tunica Intima/chemistry , Tunica Intima/innervation , Ubiquitin Thiolesterase
18.
Cardiovasc Surg ; 5(5): 481-5, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9464604

ABSTRACT

The purpose of this study was to identify whether EEG is an adequate method of monitoring cerebral perfusion during carotid endarterectomy and of determining the need for use of an indwelling shunt. A retrospective review of 305 carotid endarterectomies comparing the results of routinely shunted patients with patients selectively shunted based on EEG monitoring, was carried out. Of the carotid endarterectomies, 92 (30%) were routinely shunted and 213 (70%) were selectively shunted. In the selectively shunted group, 34 (16%) subsequently required shunting. The major stroke rate in the routinely shunted group was 4.4% ((4) cases) and in the selectively shunted group was 0.5% ((1) stroke). Three of the four major strokes in the routinely shunted group were embolic in origin and one was caused by acute thrombosis. The only major stroke in the selectively shunted group was from intracerebral hemorrhage. In conclusion EEG monitoring is a safe and reliable method to determine the need for shunting during carotid endarterectomy. Routine non-selective use of a shunt may increase the risk of perioperative stroke from arterial injury and associated thromboembolism.


Subject(s)
Electroencephalography , Endarterectomy, Carotid , Monitoring, Intraoperative/methods , Aged , Case-Control Studies , Cerebrovascular Circulation , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/prevention & control , Female , Humans , Intraoperative Care/methods , Male , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Retrospective Studies
19.
Eur J Vasc Endovasc Surg ; 14(6): 451-6, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9467519

ABSTRACT

OBJECTIVES: This study investigated the reliability of carotid duplex ultrasound (DUS) to identify appropriate candidates for carotid endarterectomy (CEA) according to a panel of vascular specialists. DESIGN: Prospective study. MATERIAL: 102 patients with 145 carotid bifurcation stenosis or occlusions. METHODS: All patients who required a carotid angiogram were evaluated using DUS followed by carotid angiography. A blinded panel of four vascular specialists individually decided whether CEA would be appropriate for each patient based on pre-angiographic information. Angiograms were then shown to panelists to see if their management decision was altered by the angiogram. RESULTS: For stenosis > or = 80% on DUS (n = 60), panelists unanimously agreed on CEA without angiography in 57 lesions. In 50 lesions (87.7%), angiography showed > or = 70% stenosis and the management plan remained unchanged. For the other seven lesions, intracranial aneurysms (n = 2), tandem intracranial lesion (n = 1), unsuspected proximal common carotid lesion (n = 1), a 40% stenotic lesion (n = 1), and high carotid bifurcations (n = 2) were seen. In lesions with 50-79% stenosis on DUS (n = 66), none of the panelists recommended CEA without prior angiography. Eighteen (27%) of these lesions were > or = 70% stenosed on angiogram. Complications of angiograms included one stroke, one haematoma, and one severe allergic reaction. CONCLUSION: Carotid duplex ultrasonography without angiography can reliably select lesions appropriate for surgery only when critical stenosis > or = 80% is chosen. Routine angiography is recommended for carotid stenosis of 50-79% when CEA is considered.


Subject(s)
Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Endarterectomy, Carotid , Cerebral Angiography , Humans , Patient Selection , Prospective Studies , Reproducibility of Results , Ultrasonography
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